View source for Biology:Rotavirus

{{Short description|Specific genus of RNA viruses}}
{{Virusbox
| image              = Rotavirus Reconstruction.jpg
| image_caption      = Computer–aided reconstruction of a rotavirus based on several electron micrographs
| image_alt          = A single particle; it is spherical and has regularly spaced, short protrusions on its surface
| taxon              = Rotavirus
| subdivision_ranks  = Species
| subdivision        = *''Rotavirus A''
* ''Rotavirus B''
* ''Rotavirus C''
* ''Rotavirus D''
* ''Rotavirus F''
* ''Rotavirus G''
* ''Rotavirus H''
* ''Rotavirus I''
* ''Rotavirus J''
}}

'''Rotaviruses''' are the most common cause of [[Medicine:Diarrhea|diarrhoeal disease]]<!-- This is not a typo. Please note this article is in British English. See WP:ENGVAR for why it should not be "fixed"to American spelling. Thanks --> among infants and young children.<ref name="pmid26337738">{{cite journal |vauthors=Dennehy PH |title=Rotavirus Infection: A Disease of the Past? |journal=Infectious Disease Clinics of North America |volume=29 |issue=4 |pages=617–635 |date=September 2015 |doi=10.1016/j.idc.2015.07.002|pmid=26337738 }}</ref> Nearly every child in the world is infected with a rotavirus at least once by the age of five.<ref name="pmid19252423" /> [[Medicine:Immunity (medical)|Immunity]] develops with each infection, so subsequent infections are less severe. Adults are rarely affected.<ref name="pmid18838873" /> ''Rotavirus'' is a [[Biology:Genus|genus]] of [[Biology:Double-stranded RNA viruses|double-stranded RNA viruses]] in the family ''Reoviridae''.There are nine [[Biology:Species|species]] of the genus, referred to as A, B, C, D, F, G, H, I and J. ''Rotavirus A'', the most common species, causes more than 90% of rotavirus infections in humans.<ref name="pmid16418157" />

The virus is transmitted by the [[Biology:Fecal–oral route|faecal–oral route]]. It infects and damages the [[Biology:Enterocyte|cells]] that line the [[Biology:Small intestine|small intestine]] and causes [[Medicine:Gastroenteritis|gastroenteritis]] (which is often called "stomach flu" despite having no relation to [[Medicine:Influenza|influenza]]). Although rotavirus was discovered in 1973 by Ruth Bishop and her colleagues by electron micrograph images<ref name="pmid19799704" /> and accounts for approximately one third of hospitalisations for severe diarrhoea in infants and children,<ref name="pmid34904636">{{cite journal |vauthors=Hallowell BD, Chavers T, Parashar U, Tate JE |title=Global Estimates of Rotavirus Hospitalizations Among Children Below 5 Years in 2019 and Current and Projected Impacts of Rotavirus Vaccination |journal=Journal of the Pediatric Infectious Diseases Society |volume=11 |issue=4 |pages=149–158 |date=April 2022 |pmid=34904636 |doi=10.1093/jpids/piab114|doi-access=free }}</ref> its importance has historically been underestimated within the public health community, particularly in [[Finance:Developing country|developing countries]].<ref name="pmid17919334">{{cite journal|year=2007|title=Use of formative research in developing a knowledge translation approach to rotavirus vaccine introduction in developing countries|journal=BMC Public Health|volume=7|page=281|doi=10.1186/1471-2458-7-281|vauthors=Simpson E, Wittet S, Bonilla J, Gamazina K, Cooley L, Winkler JL|pmid=17919334 |pmc=2173895 |s2cid=424503 |doi-access=free }}</ref> In addition to its impact on human health, rotavirus also infects other animals, and is a [[Biology:Pathogen|pathogen]] of livestock.<ref name="isbn0-12-375158-6" />

Rotaviral enteritis is usually an easily managed disease of childhood, but among children under 5 years of age rotavirus caused an estimated 151,714 deaths from diarrhoea in 2019.<ref name="pmid35643565">{{cite journal |vauthors=Janko MM, Joffe J, Michael D, Earl L, Rosettie KL, Sparks GW, Albertson SB, Compton K, Pedroza Velandia P, Stafford L, Zheng P, Aravkin A, Kyu HH, Murray CJ, Weaver MR |title=Cost-effectiveness of rotavirus vaccination in children under five years of age in 195 countries: A meta-regression analysis |journal=Vaccine |volume=40 |issue=28 |pages=3903–3917 |date=June 2022 |pmid=35643565 |doi=10.1016/j.vaccine.2022.05.042|pmc=9208428 |s2cid=249072461 }}</ref> In the United States, before initiation of the [[Medicine:Rotavirus vaccine|rotavirus vaccination]] programme in the 2000s, rotavirus caused about 2.7{{nbsp}}million cases of severe gastroenteritis in children, almost 60,000 hospitalisations, and around 37 deaths each year.<ref name="pmid17357047">{{cite journal | vauthors = Fischer TK, Viboud C, Parashar U, Malek M, Steiner C, Glass R, Simonsen L | title = Hospitalizations and deaths from diarrhea and rotavirus among children <5 years of age in the United States, 1993–2003 | journal = The Journal of Infectious Diseases | volume = 195 | issue = 8 | pages = 1117–1125 | date = April 2007 | pmid = 17357047 | doi = 10.1086/512863 | doi-access = free }}</ref> Following rotavirus vaccine introduction in the United States, hospitalisation rates have fallen significantly.<ref name=":1">{{cite journal | vauthors = Leshem E, Moritz RE, Curns AT, Zhou F, Tate JE, Lopman BA, Parashar UD | title = Rotavirus vaccines and health care utilization for diarrhea in the United States (2007–2011) | journal = Pediatrics | volume = 134 | issue = 1 | pages = 15–23 | date = July 2014 | pmid = 24913793 | doi = 10.1542/peds.2013-3849 | pmc = 7975848 | doi-access = free }}</ref><ref name="pmid21183842">{{cite journal | vauthors = Tate JE, Cortese MM, Payne DC, Curns AT, Yen C, Esposito DH, Cortes JE, Lopman BA, Patel MM, Gentsch JR, Parashar UD | s2cid = 20940659 | display-authors = 6 | title = Uptake, impact, and effectiveness of rotavirus vaccination in the United States: review of the first 3 years of postlicensure data | journal = The Pediatric Infectious Disease Journal | volume = 30 | issue = 1 Suppl | pages = S56–60 | date = January 2011 | pmid = 21183842 | doi = 10.1097/INF.0b013e3181fefdc0 | doi-access = free }}</ref> Public health campaigns to combat rotavirus focus on providing [[Medicine:Oral rehydration therapy|oral rehydration therapy]] for infected children and [[Biology:Vaccination|vaccination]] to prevent the disease.<ref name="pmid18026034" /> The incidence and severity of rotavirus infections has declined significantly in countries that have added rotavirus vaccine to their routine childhood [[Medicine:Vaccination policy|immunisation policies]].<ref name="pmid21734466" /><ref name="pmid20622508">{{cite journal | vauthors = Jiang V, Jiang B, Tate J, Parashar UD, Patel MM | title = Performance of rotavirus vaccines in developed and developing countries | journal = Human Vaccines | volume = 6 | issue = 7 | pages = 532–42 | date = July 2010 | pmid = 20622508 | pmc = 3322519 | doi = 10.4161/hv.6.7.11278 }}</ref><ref name=":2">{{cite journal | vauthors = Parashar UD, Johnson H, Steele AD, Tate JE | title = Health Impact of Rotavirus Vaccination in Developing Countries: Progress and Way Forward | journal = Clinical Infectious Diseases | volume = 62 | issue = Suppl 2 | pages = S91–95 | date = May 2016 | pmid = 27059361 | doi = 10.1093/cid/civ1015 | veditors = Parashar UD, Tate JE| doi-access = free }}</ref>

== Virology ==

=== Types of rotavirus ===
There are nine species of rotavirus, referred to as A, B, C, D, F, G, H, I and J.<ref>{{cite web|url=https://ictv.global/taxonomy|title=Virus Taxonomy: 2021 Release|publisher=International Committee on Taxonomy of Viruses (ICTV)|access-date=May 19, 2022}}</ref><ref name="pmid31447474">{{cite journal |vauthors=Suzuki H |title=Rotavirus Replication: Gaps of Knowledge on Virus Entry and Morphogenesis |journal=The Tohoku Journal of Experimental Medicine |volume=248 |issue=4 |pages=285–296 |date=August 2019 |pmid=31447474 |doi=10.1620/tjem.248.285 |doi-access=free }}</ref> Humans are primarily infected by the species ''Rotavirus A''. A–I species cause disease in other animals,<ref name="pmid20684716">{{cite journal | vauthors = Kirkwood CD | title = Genetic and antigenic diversity of human rotaviruses: potential impact on vaccination programs | journal = The Journal of Infectious Diseases | volume = 202 Suppl | issue = Suppl 1 | pages = S43–48 | date = September 2010 | pmid = 20684716 | doi = 10.1086/653548 | doi-access = free }}</ref> species H in pigs, D, F and G in birds, I in cats and J in bats.<ref name="pmid21801631">{{cite journal | vauthors = Wakuda M, Ide T, Sasaki J, Komoto S, Ishii J, Sanekata T, Taniguchi K | title = Porcine rotavirus closely related to novel group of human rotaviruses | journal = Emerging Infectious Diseases | volume = 17 | issue = 8 | pages = 1491–1493 | date = August 2011 | pmid = 21801631 | pmc = 3381553 | doi = 10.3201/eid1708.101466 }}</ref><ref name="pmid24960190">{{cite journal | vauthors = Marthaler D, Rossow K, Culhane M, Goyal S, Collins J, Matthijnssens J, Nelson M, Ciarlet M | title = Widespread rotavirus H in commercially raised pigs, United States | journal = Emerging Infectious Diseases | volume = 20 | issue = 7 | pages = 1195–1198 | date = July 2014 | pmid = 24960190 | pmc = 4073875 | doi = 10.3201/eid2007.140034 }}</ref><ref>{{cite journal | vauthors = Phan TG, Leutenegger CM, Chan R, Delwart E | title = Rotavirus I in feces of a cat with diarrhea | journal = Virus Genes | volume = 53 | issue = 3 | pages = 487–490 | date = June 2017 | pmid = 28255929 | doi = 10.1007/s11262-017-1440-4 | pmc = 7089198 }}</ref><ref name="pmid27932285">{{cite journal |vauthors=Bányai K, Kemenesi G, Budinski I, Földes F, Zana B, Marton S, Varga-Kugler R, Oldal M, Kurucz K, Jakab F |title=Candidate new rotavirus species in Schreiber's bats, Serbia |journal=Infection, Genetics and Evolution |volume=48 |pages=19–26 |date=March 2017 |pmid=27932285 |doi=10.1016/j.meegid.2016.12.002 |pmc=7106153 }}</ref>

Within the species ''Rotavirus A'' there are different strains, called serotypes.<ref name="pmid19252426">{{cite journal | vauthors = O'Ryan M | title = The ever-changing landscape of rotavirus serotypes | journal = The Pediatric Infectious Disease Journal | volume = 28 | issue = 3 Suppl | pages = S60–62 | date = March 2009 | pmid = 19252426 | doi = 10.1097/INF.0b013e3181967c29 | s2cid = 22421988 | doi-access = free }}</ref> As with [[Medicine:Influenza|influenza]] virus, a dual classification system is used based on two proteins on the surface of the virus. The [[Chemistry:Glycoprotein|glycoprotein]] VP7 defines the G serotypes and the [[Biology:Protease|protease]]-sensitive protein VP4 defines P serotypes.<ref name="pmid22284787">{{cite journal | vauthors = Patton JT | title = Rotavirus diversity and evolution in the post-vaccine world | journal = Discovery Medicine | volume = 13 | issue = 68 | pages = 85–97 | date = January 2012 | pmid = 22284787 | pmc = 3738915 | url = http://www.discoverymedicine.com/John-T-Patton/2012/01/26/rotavirus-diversity-and-evolution-in-the-post-vaccine-world/ }}</ref> Because the two genes that determine G-types and P-types can be passed on separately to progeny viruses, different combinations are found.<ref name="pmid22284787" /> A whole genome genotyping system has been established for ''Rotavirus A'', which has been used to determine the origin of atypical strains.<ref name="pmid28748110">{{cite journal | vauthors = Phan MV, Anh PH, Cuong NV, Munnink BB, van der Hoek L, My PT, Tri TN, Bryant JE, Baker S, Thwaites G, Woolhouse M, Kellam P, Rabaa MA, Cotten M | title = Unbiased whole-genome deep sequencing of human and porcine stool samples reveals circulation of multiple groups of rotaviruses and a putative zoonotic infection | journal = Virus Evolution | volume = 2 | issue = 2 | pages = vew027 | date = July 2016 | pmid = 28748110 | pmc = 5522372 | doi = 10.1093/ve/vew027 }}</ref> The prevalence of the individual G-types and P-types varies between, and within, countries and years.<ref name="pmid2556435">{{cite journal | vauthors = Beards GM, Desselberger U, Flewett TH | title = Temporal and geographical distributions of human rotavirus serotypes, 1983 to 1988 | journal = Journal of Clinical Microbiology | volume = 27 | issue = 12 | pages = 2827–2833 | date = December 1989 | pmid = 2556435 | pmc = 267135 | doi =  10.1128/JCM.27.12.2827-2833.1989}}</ref> There are at least 36 G types and 51 P types<ref name="pmid33482744">{{cite journal |vauthors=Rakau KG, Nyaga MM, Gededzha MP, Mwenda JM, Mphahlele MJ, Seheri LM, Steele AD |title=Genetic characterization of G12P[6] and G12P[8] rotavirus strains collected in six African countries between 2010 and 2014 |journal=BMC Infectious Diseases |volume=21 |issue=1 |pages=107 |date=January 2021 |pmid=33482744 |pmc=7821174 |doi=10.1186/s12879-020-05745-6 |doi-access=free }}</ref> but in infections of humans only a few combinations of G and P types predominate. They are G1P[8], G2P[4], G3P[8], G4P[8], G9P[8] and G12P[8].<ref name="pmid38015834">{{cite journal |vauthors=Antoni S, Nakamura T, Cohen AL, Mwenda JM, Weldegebriel G, Biey JN, Shaba K, Rey-Benito G, de Oliveira LH, Oliveira MT, Ortiz C, Ghoniem A, Fahmy K, Ashmony HA, Videbaek D, Daniels D, Pastore R, Singh S, Tondo E, Liyanage JB, Sharifuzzaman M, Grabovac V, Batmunkh N, Logronio J, Armah G, Dennis FE, Seheri M, Magagula N, Mphahlele J, Leite JP, Araujo IT, Fumian TM, El Mohammady H, Semeiko G, Samoilovich E, Giri S, Kang G, Thomas S, Bines J, Kirkwood CD, Liu N, Lee DY, Iturriza-Gomara M, Page NA, Esona MD, Ward ML, Wright CN, Mijatovic-Rustempasic S, Tate JE, Parashar UD, Gentsch J, Bowen MD, Serhan F |title=Rotavirus genotypes in children under five years hospitalized with diarrhea in low and middle-income countries: Results from the WHO-coordinated Global Rotavirus Surveillance Network |journal=PLOS Global Public Health |volume=3 |issue=11 |pages=e0001358 |date=2023 |pmid=38015834 |pmc=10683987 |doi=10.1371/journal.pgph.0001358 |doi-access=free }}</ref>

=== Structure ===
The [[Biology:Genome|genome]] of rotaviruses consists of 11 unique double helix molecules of [[Biology:RNA|RNA]] (dsRNA) which are 18,555 nucleotides in total. Each helix, or segment, is a [[Biology:Gene|gene]], numbered 1 to 11 by decreasing size. Each gene codes for one [[Biology:Protein|protein]], except genes 9, which codes for two.<ref name="pmid2556635">{{cite journal |vauthors=Estes MK, Cohen J |title=Rotavirus gene structure and function |journal=Microbiological Reviews |volume=53 |issue=4 |pages=410–449 |year=1989 |pmid=2556635 |pmc=372748 |doi= 10.1128/MMBR.53.4.410-449.1989}}</ref> The RNA is surrounded by a three-layered [[Truncated icosahedron|icosahedral]] protein [[Biology:Capsid|capsid]]. Viral particles are up to 76.5{{nbsp}}nm in diameter<ref name="pmid16913048">{{cite book |veditors=Roy P |vauthors=Pesavento JB, Crawford SE, Estes MK, Prasad BV |chapter=Rotavirus proteins: structure and assembly |volume=309 |pages=189–219 |year=2006 |pmid=16913048 |doi=10.1007/3-540-30773-7_7 |series=Current Topics in Microbiology and Immunology |title=Reoviruses: Entry, Assembly and Morphogenesis |isbn=978-3-540-30772-3|publisher=Springer|location=New York|s2cid=11290382 }}</ref><ref name="pmid8050286">{{cite book |vauthors=Prasad BV, Chiu W |chapter=Structure of Rotavirus |veditors=Ramig RF |series=Current Topics in Microbiology and Immunology|title=Rotaviruses |volume=185 |pages=9–29 |year=1994 |pmid=8050286|publisher=Springer|location=New York|isbn=978-3-540-56761-5|doi=10.1007/978-3-642-78256-5_2 }}</ref> and are not [[Biology:Viral envelope|enveloped]].<ref name="pmid31317495">{{cite book |vauthors=Rodríguez JM, Luque D |title=Physical Virology |chapter=Structural Insights into Rotavirus Entry |series=Advances in Experimental Medicine and Biology |volume=1215|pages=45–68 |date=2019 |pmid=31317495 |doi=10.1007/978-3-030-14741-9_3|hdl=20.500.12105/10344 |isbn=978-3-030-14740-2 |s2cid=197541267 |hdl-access=free }}</ref>

=== Proteins ===
[[File:Rotavirus Structure.png|thumb|A simplified diagram of the location of rotavirus structural proteins<ref>{{cite book | last1=Gray | first1=James | last2=Desselberger | first2=U. | title=Rotaviruses : methods and protocols | publisher=Humana Press | publication-place=Totowa, N.J. | date=2000 | isbn=978-1-59259-078-0 | oclc=55684328 | page=15}}</ref>|alt=A cut-up image of a single rotavirus particle showing the RNA molecules surrounded by the VP6 protein and this in turn surrounded by the VP7 protein. The VP4 protein protrudes from the surface of the spherical particle.]]
There are six viral proteins (VPs) that form the virus particle (virion). These ''structural'' proteins are called VP1, VP2, VP3, VP4, VP6 and VP7. In addition to the VPs, there are six ''nonstructural'' proteins (NSPs), that are only produced in cells infected by rotavirus. These are called [[Biology:NSP1 (rotavirus)|NSP1]], NSP2, NSP3, NSP4, NSP5 and NSP6.<ref name="pmid20684716" />

At least six of the twelve proteins [[Biology:Coding region|encoded]] by the rotavirus genome bind [[Biology:RNA|RNA]].<ref name="pmid7595370">{{cite journal |vauthors=Patton JT |title=Structure and function of the rotavirus RNA-binding proteins |journal=The Journal of General Virology |volume=76 |issue= 11|pages=2633–2644 |year=1995 |pmid=7595370 |doi=10.1099/0022-1317-76-11-2633 |doi-access=free }}</ref> The role of these proteins in rotavirus replication is not entirely understood; their functions are thought to be related to RNA synthesis and packaging in the virion, mRNA transport to the site of genome replication, and [[Biology:Messenger RNA|mRNA]] translation and regulation of gene expression.<ref name="pmid11444036">{{cite book |author=Patton JT |chapter=Rotavirus RNA Replication and Gene Expression |title=Gastroenteritis Viruses |volume=238 |pages=64–77; discussion 77–81 |year=2001 |pmid=11444036 |doi=10.1002/0470846534.ch5 |series=Novartis Foundation Symposia |isbn=978-0-470-84653-7}}</ref>

==== Structural proteins ====
[[File:Rotavirus with gold- labelled monoclonal antibody.jpg|thumb|Electron micrograph of gold nanoparticles attached to rotavirus. The small dark circular objects are gold nanoparticles coated with a [[Biology:Monoclonal antibody|monoclonal antibody]] specific for rotavirus protein VP6.|alt=An electron micrograph of many rotavirus particles, two of which have several smaller, black spheres which appear to be attached to them|left]]VP1 is located in the core of the virus particle and is an RNA-dependent RNA polymerase [[Biology:Enzyme|enzyme]].<ref name="pmid17657346">{{cite journal |vauthors=Vásquez-del Carpió R, Morales JL, Barro M, Ricardo A, Spencer E |title=Bioinformatic prediction of polymerase elements in the rotavirus VP1 protein |journal=Biological Research |volume=39 |issue=4 |pages=649–659 |year=2006 |pmid=17657346 |doi=10.4067/S0716-97602006000500008 |doi-access=free }}</ref> In an infected cell this enzyme produces mRNA transcripts for the synthesis of viral proteins and produces copies of the rotavirus genome RNA segments for newly produced virus particles.<ref name="pmid22595300">{{cite journal |vauthors=Trask SD, Ogden KM, Patton JT |title=Interactions among capsid proteins orchestrate rotavirus particle functions |journal=Current Opinion in Virology |volume=2 |issue=4 |pages=373–379 |year=2012 |pmid=22595300 |pmc=3422376 |doi=10.1016/j.coviro.2012.04.005 }}</ref>

VP2 forms the core layer of the virion and binds the RNA genome.<ref name="pmid15010217">{{cite journal |vauthors=Taraporewala ZF, Patton JT |title=Nonstructural proteins involved in genome packaging and replication of rotaviruses and other members of the Reoviridae |journal=Virus Research |volume=101 |issue=1 |pages=57–66 |year=2004 |pmid=15010217 |doi=10.1016/j.virusres.2003.12.006 |url=https://zenodo.org/record/1259439}}</ref>

VP3 is part of the inner core of the virion and is an enzyme called guanylyl transferase. This is a [[Biology:Capping enzyme|capping enzyme]] that catalyses the formation of the 5' cap in the [[Biology:Post-transcriptional modification|post-transcriptional modification]] of mRNA.<ref name="isbn0-12-375147-02">{{cite book |vauthors=Angel J, Franco MA, Greenberg HB |veditors=Mahy BW, Van Regenmortel MH |title=Desk Encyclopedia of Human and Medical Virology |publisher=Academic Press |location=Boston |year=2009 |page=277 |isbn=978-0-12-375147-8}}</ref> The cap stabilises viral mRNA by protecting it from [[Biology:Nucleic acid|nucleic acid]] degrading enzymes called nucleases.<ref name="pmid20025612">{{cite journal |vauthors=Cowling VH |title=Regulation of mRNA cap methylation |journal=The Biochemical Journal |volume=425 |issue=2 |pages=295–302 |year=2009 |pmid=20025612 |pmc=2825737 |doi=10.1042/BJ20091352 }}</ref>

VP4 is on the surface of the virion that protrudes as a spike.<ref name="pmid16571811">{{cite journal |vauthors=Gardet A, Breton M, Fontanges P, Trugnan G, Chwetzoff S |title=Rotavirus spike protein VP4 binds to and remodels actin bundles of the epithelial brush border into actin bodies |journal=Journal of Virology |volume=80 |issue=8 |pages=3947–3456 |year=2006 |pmid=16571811 |doi=10.1128/JVI.80.8.3947-3956.2006 |pmc=1440440}}</ref> It binds to molecules on the surface of cells called [[Biology:Receptor (biochemistry)|receptors]] and drives the entry of the virus into the cell.<ref name="pmid12234525">{{cite journal |vauthors=Arias CF, Isa P, Guerrero CA, Méndez E, Zárate S, López T, Espinosa R, Romero P, López S |title=Molecular biology of rotavirus cell entry |journal=Archives of Medical Research |volume=33 |issue=4 |pages=356–361 |year=2002 |pmid=12234525 |doi=10.1016/S0188-4409(02)00374-0}}</ref> VP4 has to be modified by the [[Biology:Protease|protease]] enzyme [[Biology:Trypsin|trypsin]], which is found in the gut, into VP5* and VP8* before the virus is infectious.<ref name="pmid15010218">{{cite journal |vauthors=Jayaram H, Estes MK, Prasad BV |title=Emerging themes in rotavirus cell entry, genome organization, transcription and replication |journal=Virus Research |volume=101 |issue=1 |pages=67–81 |year=2004 |pmid=15010218 |doi=10.1016/j.virusres.2003.12.007}}</ref> VP4 determines how virulent the virus is and it determines the P-type of the virus.<ref name="pmid12167342">{{cite journal |vauthors=Hoshino Y, Jones RW, Kapikian AZ |title=Characterization of neutralization specificities of outer capsid spike protein VP4 of selected murine, lapine, and human rotavirus strains |journal=Virology |volume=299 |issue=1 |pages=64–71 |year=2002 |pmid=12167342 |doi=10.1006/viro.2002.1474|doi-access=free }}</ref> In humans there is an association between the blood group ([[Medicine:Lewis antigen system|Lewis antigen system]], [[Biology:ABO blood group system|ABO blood group system]] and [[Medicine:Secretor status|secretor status]]) and susceptibility to infection. Non-secretors seem resistant to infection by types P[4] and P[8], indicating that blood group antigens are the receptors for these genotypes.<ref name="pmid24523471">{{cite journal |vauthors=Van Trang N, Vu HT, Le NT, Huang P, Jiang X, Anh DD |title=Association between norovirus and rotavirus infection and histo-blood group antigen types in Vietnamese children |journal=Journal of Clinical Microbiology |volume=52 |issue=5 |pages=1366–1374 |year=2014 |pmid=24523471 |pmc=3993640 |doi=10.1128/JCM.02927-13 }}</ref> This resistance is dependent on the rotavirus genotype.<ref name="pmid32192193">{{cite journal |vauthors=Sharma S, Hagbom M, Svensson L, Nordgren J |title=The Impact of Human Genetic Polymorphisms on Rotavirus Susceptibility, Epidemiology, and Vaccine Take |journal=Viruses |volume=12 |issue=3 |date=March 2020 |page=324 |pmid=32192193 |pmc=7150750 |doi=10.3390/v12030324 |url=|doi-access=free }}</ref>

VP6 forms the bulk of the capsid. It is highly [[Biology:Antigen|antigen]]ic and can be used to identify rotavirus species.<ref name="pmid9015109" /> This protein is used in laboratory tests for rotavirus infections.<ref name="pmid6321549">{{cite journal |vauthors=Beards GM, Campbell AD, Cottrell NR, Peiris JS, Rees N, Sanders RC, Shirley JA, Wood HC, Flewett TH |title=Enzyme-linked immunosorbent assays based on polyclonal and monoclonal antibodies for rotavirus detection |journal=Journal of Clinical Microbiology |volume=19 |issue=2 |pages=248–54 |year=1984|doi=10.1128/JCM.19.2.248-254.1984 |pmid=6321549 |url=http://jcm.asm.org/cgi/reprint/19/2/248 |format=PDF |pmc=271031 }}</ref>

VP7 is a [[Chemistry:Glycoprotein|glycoprotein]] that forms the outer surface of the virion. Apart from its structural functions, it determines the G-type of the strain and, along with VP4, is involved in [[Medicine:Immunity (medical)|immunity]] to infection.<ref name="pmid16913048" />

==== Nonstructural viral proteins ====
NSP1, the product of gene 5, is a nonstructural RNA-binding protein.<ref>{{cite journal |vauthors=Hua J, Mansell EA, Patton JT |title=Comparative analysis of the rotavirus NS53 gene: conservation of basic and cysteine-rich regions in the protein and possible stem-loop structures in the RNA |journal=Virology |volume=196 |issue=1 |pages=372–378 |year=1993 |pmid=8395125 |doi=10.1006/viro.1993.1492|doi-access=free }}</ref> NSP1 also blocks the [[Biology:Interferon|interferon]] response, the part of the [[Biology:Innate immune system|innate immune system]] that protects cells from viral infection. NSP1 causes the proteosome to degrade key signaling components required to stimulate production of interferon in an infected cell and to respond to interferon secreted by adjacent cells.

Targets for degradation include several [[Biology:Interferon regulatory factors|IRF]] transcription factors required for interferon gene transcription.<ref name=Arnold2016>{{cite journal |vauthors=Arnold MM |title=The Rotavirus Interferon Antagonist NSP1: Many Targets, Many Questions |journal=Journal of Virology |volume=90 |issue=11 |pages=5212–5215 |year=2016 |pmid=27009959 |doi=10.1128/JVI.03068-15 |pmc=4934742 }}</ref>

NSP2 is an [[Biology:RNA-binding protein|RNA-binding protein]] that accumulates in cytoplasmic inclusions ([[Biology:Viroplasm|viroplasm]]s) and is required for genome replication.<ref>{{cite journal |vauthors=Kattoura MD, Chen X, Patton JT |title=The rotavirus RNA-binding protein NS35 (NSP2) forms 10S multimers and interacts with the viral RNA polymerase |journal=Virology |volume=202 |issue=2 |pages=803–13 |year=1994 |pmid=8030243 |doi=10.1006/viro.1994.1402|doi-access=free }}</ref><ref name="pmid15010217" />

NSP3 is bound to viral mRNAs in infected cells and it is responsible for the shutdown of cellular protein synthesis.<ref>{{cite journal |title=Rotavirus protein NSP3 (NS34) is bound to the 3' end consensus sequence of viral mRNAs in infected cells
|journal=Journal of Virology |volume=67 |issue=6 |pages=3159–3165 |year=1993|pmid=8388495 |url=http://jvi.asm.org/cgi/reprint/67/6/3159 |format=PDF |pmc=237654 |vauthors=Poncet D, Aponte C, Cohen J|doi=10.1128/JVI.67.6.3159-3165.1993 }}</ref> NSP3 inactivates two translation initiation factors essential for synthesis of proteins from host mRNA.

First, NSP3 ejects poly(A)-binding protein (PABP) from the translation initiation factor eIF4F.  PABP is required for efficient translation of transcripts with a 3' poly(A) tail, which is found on most host cell transcripts. Second, NSP3 inactivates [[Biology:EIF2|eIF2]] by stimulating its phosphorylation.<ref name="pmid26727111">{{cite journal |vauthors=Gratia M, Vende P, Charpilienne A, Baron HC, Laroche C, Sarot E, Pyronnet S, Duarte M, Poncet D |title=Challenging the Roles of NSP3 and Untranslated Regions in Rotavirus mRNA Translation |journal=PLOS ONE |volume=11 |issue=1 |pages=e0145998 |year=2016 |pmid=26727111 |pmc=4699793 |doi=10.1371/journal.pone.0145998 |bibcode=2016PLoSO..1145998G |doi-access=free }}</ref> Efficient translation of rotavirus mRNA, which lacks the 3' poly(A) tail, does not require either of these factors.<ref name="Lopez2012">{{cite journal|vauthors=López S, Arias CF|title=Rotavirus-host cell interactions: an arms race|journal=Current Opinion in Virology|year=2012|volume=2|issue=4|pages=389–398|doi=10.1016/j.coviro.2012.05.001|pmid=22658208}}</ref>

NSP4 is a viral [[Biology:Enterotoxin|enterotoxin]] that induces diarrhoea and was the first viral enterotoxin discovered.<ref name="pmid19114772">{{cite journal |vauthors=Hyser JM, Estes MK |title=Rotavirus vaccines and pathogenesis: 2008 |journal=Current Opinion in Gastroenterology |volume=25 |issue=1 |pages=36–43 |year=2009 |pmid=19114772 |pmc=2673536 |doi=10.1097/MOG.0b013e328317c897 }}</ref> It is a [[Biology:Viroporin|viroporin]] that elevates cytosolic Ca<sup>2+</sup> in mammalian cells.<ref name="pmid28256607">{{cite journal |vauthors=Pham T, Perry JL, Dosey TL, Delcour AH, Hyser JM |title=The Rotavirus NSP4 Viroporin Domain is a Calcium-conducting Ion Channel |journal=Scientific Reports |volume=7 |issue= |pages=43487 |date=March 2017 |pmid=28256607 |pmc=5335360 |doi=10.1038/srep43487 |bibcode=2017NatSR...743487P |url=}}</ref>

NSP5 is encoded by genome segment 11 of rotavirus A. In virus-infected cells NSP5 accumulates in the viroplasm.<ref>{{cite journal |vauthors=Afrikanova I, Miozzo MC, Giambiagi S, Burrone O |title=Phosphorylation generates different forms of rotavirus NSP5 |journal=Journal of General Virology |volume=77 |pages=2059–2065 |year=1996 |pmid=8811003 |doi=10.1099/0022-1317-77-9-2059 |issue=9 |doi-access=free }}</ref>

NSP6 is a nucleic acid binding protein<ref>{{cite journal |vauthors=Rainsford EW, McCrae MA |title=Characterization of the NSP6 protein product of rotavirus gene 11 |journal=Virus Research |volume=130 |issue=1–2 |pages=193–201 |year=2007 |pmid=17658646 |doi=10.1016/j.virusres.2007.06.011}}</ref> and is encoded by gene 11 from an out-of-phase [[Biology:Open reading frame|open reading frame]].<ref>{{cite journal |vauthors=Mohan KV, Atreya CD |s2cid=21538632 |title=Nucleotide sequence analysis of rotavirus gene 11 from two tissue culture-adapted ATCC strains, RRV and Wa |journal=Virus Genes |volume=23 |issue=3 |pages=321–329 |year=2001 |pmid=11778700 |doi=10.1023/A:1012577407824}}</ref>

{| class="wikitable" style="text-align:center"
|+ Rotavirus genes and proteins
! RNA Segment (Gene) !! Size ([[Biology:Base pair|base pair]]s) !! Protein !! [[Biology:UniProt|UniProt]] !! Molecular weight kDa !! Location !! Copies per particle !! Function
|-
! 1
| 3302 || VP1 || {{UniProt|P22678}} || 125 || At the vertices of the core || 12 || RNA-dependent RNA polymerase
|-
! 2
| 2690 || VP2 || {{UniProt|A2T3R5}} || 102 || Forms inner shell of the core || 120 || RNA binding
|-
! 3
| 2591 || VP3 || {{UniProt|A2T3S5}} || 88 || At the vertices of the  core || 12 || methyltransferase mRNA capping enzyme
|-
! 4
| 2362 || VP4 || {{UniProt|A2T3T2}} || 87 || Surface spike || 180 || Cell attachment, virulence
|-
!5
| 1611 || [[Biology:NSP1 (rotavirus)|NSP1]] || {{UniProt|Q99FX5}} || 59 || Nonstructural || 0 || 5'RNA binding, interferon antagonist
|-
!6
| 1356 || VP6 || {{UniProt|Q6LE89}} || 45 || Inner Capsid || 780 || Structural and species-specific antigen
|-
!7
| 1104 || NSP3 || {{UniProt|P03536}} || 37 || Nonstructural || 0 || Enhances viral mRNA activity and shut-offs  cellular protein synthesis
|-
!8
| 1059 || NSP2 || {{UniProt|A2T3P0}} || 35 || Nonstructural || 0 || NTPase involved in RNA packaging
|-
!9
| 1062 || VP7{{sup|1}} VP7{{sup|2}} || {{UniProt|P03533}} || 38 and 34 || Surface || 780 || Structural and neutralisation  antigen
|-
!10
| 751 || NSP4 || {{UniProt|P04512}} || 20 || Nonstructural || 0 || Viroporin ([[Biology:Enterotoxin|enterotoxin]])
|-
!11
| 667 || NSP5 NSP6 || {{UniProt|A2T3Q9}} {{UniProt|P11203}} || 22 || Nonstructural || 0 || ssRNA and dsRNA binding modulator of NSP2, phosphoprotein
|}
This table is based on the [[Biology:Simian|simian]] rotavirus strain SA11. RNA-protein coding assignments differ in some strains.

=== Replication ===
[[File:Rotavirus replication.png|thumb|A simplified drawing of the rotavirus replication cycle.<ref name="Gray Desselberger 2000 p. ">{{cite book | last1=Gray | first1=James | last2=Desselberger | first2=U. | title=Rotaviruses : methods and protocols | publisher=Humana Press | publication-place=Totowa, N.J. | date=2000 | isbn=978-1-59259-078-0 | oclc=55684328 | page=5}}</ref> The stages are:{{numbered list|Attachment of the virus to the host cells, which is mediated by VP4 and VP7|Penetration of the cell by the virus and uncoating of the viral capsid|Plus strand ssRNA synthesis (this acts as the mRNA) synthesis, which is mediated by VP1, VP3 and VP2|Formation of the viroplasm, viral RNA packaging and minus strand RNA synthesis and formation of the double-layered virus particles|Virus particle maturation and release of progeny virions}}]]

The attachment of the virus to the host cell is initiated by VP4, which attaches to molecules, called glycans, on the surface of the cell.<ref name="pmid31317495"/> The virus enters cells by [[Biology:Endocytosis|receptor mediated endocytosis]] and form a vesicle known as an [[Biology:Endosome|endosome]]. Proteins in the third layer (VP7 and the VP4 spike) disrupt the membrane of the endosome, creating a difference in the [[Biology:Calcium in biology|calcium]] concentration. This causes the breakdown of VP7 trimers into single protein subunits, leaving the VP2 and VP6 protein coats around the viral dsRNA, forming a double-layered particle (DLP).<ref name="pmid20397068">{{cite book |vauthors=Baker M, Prasad BV |chapter=Rotavirus cell entry |series=Current Topics in Microbiology and Immunology |title=Cell Entry by Non-Enveloped Viruses |volume=343 |pages=121–148 |year=2010 |pmid=20397068 |doi=10.1007/82_2010_34 |isbn=978-3-642-13331-2 |veditors=Johnson J}}</ref>

The eleven dsRNA strands remain within the protection of the two protein shells and the viral RNA-dependent RNA polymerase creates mRNA transcripts of the double-stranded viral genome. By remaining in the core, the viral RNA evades innate host immune responses including [[Biology:RNA interference|RNA interference]] that are triggered by the presence of double-stranded RNA.<ref name="pmid27009959">{{cite journal |vauthors=Arnold MM |title=The Rotavirus Interferon Antagonist NSP1: Many Targets, Many Questions |journal=Journal of Virology |volume=90 |issue=11 |pages=5212–5215 |year=2016 |pmid=27009959 |pmc=4934742 |doi=10.1128/JVI.03068-15 }}</ref>

During the infection, rotaviruses produce mRNA for both [[Biology:Protein biosynthesis|protein biosynthesis]] and gene replication. Most of the rotavirus proteins accumulate in viroplasm, where the RNA is replicated and the DLPs are assembled. In the viroplasm the positive sense viral RNAs that are used as templates for the synthesis of viral genomic dsRNA are protected from siRNA-induced RNase degradation.<ref name="pmid15220450">{{cite journal |vauthors=Silvestri LS, Taraporewala ZF, Patton JT |title=Rotavirus replication: plus-sense templates for double-stranded RNA synthesis are made in viroplasms |journal=Journal of Virology |volume=78 |issue=14 |pages=7763–7774 |year=2004 |pmid=15220450 |pmc=434085 |doi=10.1128/JVI.78.14.7763-7774.2004 }}</ref> Viroplasm is formed around the cell nucleus as early as two hours after virus infection, and consists of viral factories thought to be made by two viral nonstructural proteins: NSP5 and NSP2. Inhibition of NSP5 by RNA interference ''in vitro'' results in a sharp decrease in rotavirus replication. The DLPs migrate to the endoplasmic reticulum where they obtain their third, outer layer (formed by VP7 and VP4). The [[Biology:Offspring|progeny]] viruses are released from the cell by lysis.<ref name="pmid15010218" /><ref name="pmid15579070">{{cite journal |vauthors=Patton JT, Vasquez-Del Carpio R, Spencer E |title=Replication and transcription of the rotavirus genome |journal=Current Pharmaceutical Design |volume=10 |issue=30 |pages=3769–3777 |year=2004 |pmid=15579070 |doi=10.2174/1381612043382620}}</ref><ref name="pmid20024520">{{cite journal |vauthors=Ruiz MC, Leon T, Diaz Y, Michelangeli F |title=Molecular biology of rotavirus entry and replication |journal=The Scientific World Journal |volume=9|pages=1476–1497 |year=2009 |pmid=20024520 |pmc=5823125 |doi=10.1100/tsw.2009.158 |doi-access=free }}</ref>

== Transmission ==
[[File:Multiple rotavirus particles.jpg|thumb|Rotaviruses in the faeces of an infected child|alt=Many rotavirus particles packed together, which all look similar]]

Rotaviruses are transmitted by the [[Biology:Fecal–oral route|faecal–oral route]], via contact with contaminated hands, surfaces and objects,<ref name="pmid8393172">{{cite journal
|vauthors=Butz AM, Fosarelli P, Dick J, Cusack T, Yolken R |title=Prevalence of rotavirus on high-risk fomites in day-care facilities
|journal=Pediatrics
|volume=92
|issue=2
|pages=202–205
|year=1993
|doi=10.1542/peds.92.2.202
|pmid=8393172
|s2cid=20327842
}}</ref> and possibly by the respiratory route.<ref name="pmid11052397">{{cite journal
|author=Dennehy PH
|s2cid=28625697
|title=Transmission of rotavirus and other enteric pathogens in the home
|journal=Pediatric Infectious Disease Journal
|volume=19
|issue=Suppl 10
|pages=S103–105
|year=2000
|pmid=11052397
|doi=10.1097/00006454-200010001-00003
|doi-access=free
}}</ref> Viral diarrhoea is highly contagious. The faeces of an infected person can contain more than 10 trillion infectious particles per gram;<ref name="pmid9015109" /> fewer than 100 of these are required to transmit infection to another person.<ref name="pmid18838873">{{cite journal |vauthors=Grimwood K, Lambert SB |s2cid=31164630 |title=Rotavirus vaccines: opportunities and challenges |journal=Human Vaccines |volume=5 |issue=2 |pages=57–69 |year=2009 |pmid=18838873 |doi=10.4161/hv.5.2.6924 |url=http://www.landesbioscience.com/journals/hv/abstract.php?id=6924|doi-access=free }}</ref>

Rotaviruses are stable in the environment and have been found in [[Earth:Estuary|estuary]] samples at levels up to 1–5 infectious particles per US{{nbsp}}gallon. The viruses survive between 9 and 19 days.<ref name="pmid6091548">{{cite journal |vauthors=Rao VC, Seidel KM, Goyal SM, Metcalf TG, Melnick JL |title=Isolation of enteroviruses from water, suspended solids, and sediments from Galveston Bay: survival of poliovirus and rotavirus adsorbed to sediments |journal=Applied and Environmental Microbiology |volume=48 |issue=2 |pages=404–409 |year=1984|doi=10.1128/AEM.48.2.404-409.1984 |pmid=6091548 |url=http://aem.asm.org/cgi/reprint/48/2/404 |format=PDF |pmc=241526 |bibcode=1984ApEnM..48..404R }}</ref> Sanitary measures adequate for eliminating [[Biology:Bacteria|bacteria]] and [[Biology:Parasite|parasite]]s seem to be ineffective in control of rotavirus, as the incidence of rotavirus infection in countries with high and low health standards is similar.<ref name="pmid11052397" />

== Signs and symptoms ==

Rotaviral enteritis is a mild to severe disease characterised by nausea, [[Medicine:Vomiting|vomiting]], watery diarrhoea and low-grade [[Medicine:Fever|fever]]. Once a child is infected by the virus, there is an [[Medicine:Incubation period|incubation period]] of about two days before symptoms appear.<ref name="pmid10532018">{{cite journal |vauthors=Hochwald C, Kivela L |title=Rotavirus vaccine, live, oral, tetravalent (RotaShield) |journal=Pediatric Nursing |volume=25 |issue=2 |pages=203–204, 207 |year=1999|pmid=10532018}}</ref> The period of illness is acute. Symptoms often start with vomiting followed by four to eight days of profuse diarrhoea. [[Medicine:Dehydration|Dehydration]] is more common in rotavirus infection than in most of those caused by bacterial pathogens, and is the most common cause of death related to rotavirus infection.<ref name="pmid1962726">{{cite journal |vauthors=Maldonado YA, Yolken RH |title=Rotavirus |journal=Baillière's Clinical Gastroenterology |volume=4 |issue=3 |pages=609–625 |year=1990 |pmid=1962726 |doi=10.1016/0950-3528(90)90052-I }}</ref>

Rotavirus infections can occur throughout life: the first usually [[Medicine:Symptom#Types|produces symptoms]], but subsequent infections are typically mild or [[Medicine:Asymptomatic|asymptomatic]],<ref name="pmid16860702">{{cite journal |vauthors=Glass RI, Parashar UD, Bresee JS, Turcios R, Fischer TK, Widdowson MA, Jiang B, Gentsch JR |s2cid=34569166 |title=Rotavirus vaccines: current prospects and future challenges |journal=The Lancet |volume=368 |issue=9532 |pages=323–332 |year= 2006 |pmid=16860702 |doi=10.1016/S0140-6736(06)68815-6 }}</ref><ref name="pmid9015109">{{cite journal |vauthors=Bishop RF |title=Natural history of human rotavirus infection |journal=Archives of Virology. Supplementum |volume=12 |issue= |pages=119–28 |date=1996 |pmid=9015109 |doi=10.1007/978-3-7091-6553-9_14}}</ref> as the immune system provides some protection.<ref name="isbn0-471-49663-43">{{cite book |author=Offit PA|title=Gastroenteritis viruses|isbn=978-0-471-49663-2 |publisher=Wiley |location=New York |year=2001 |pages=106–124}}</ref> Consequently, symptomatic infection rates are highest in children under two years of age and decrease progressively towards 45 years of age.<ref name="isbn0-89603-736-32">{{cite book |vauthors=Ramsay M, Brown D |veditors=Desselberger U, Gray J |title=Rotaviruses: Methods and Protocols|series=Methods in Molecular Medicine|volume=34|pages=217–238 |publisher=Humana Press |location=Totowa, NJ |year=2000|isbn=978-0-89603-736-6|chapter=Epidemiology of Group A Rotaviruses: Surveillance and Burden of Disease Studies|doi=10.1385/1-59259-078-0:217|pmid=21318862}}</ref> The most severe symptoms tend to occur in children six months to two years of age, the elderly, and those with immunodeficiency. Due to immunity acquired in childhood, most adults are not susceptible to rotavirus; gastroenteritis in adults usually has a cause other than rotavirus, but asymptomatic infections in adults may maintain the transmission of infection in the community.<ref name="pmid14871633">{{cite journal |vauthors=Anderson EJ, Weber SG |title=Rotavirus infection in adults |journal=The Lancet Infectious Diseases |volume=4 |issue=2 |pages=91–99 |year=2004 |pmid=14871633 |doi=10.1016/S1473-3099(04)00928-4 |pmc=7106507 }}</ref> There is some evidence to suggest blood group can impact on the susceptibility to infection by rotaviruses.<ref name="pmid32918943">{{cite journal |vauthors=Elhabyan A, Elyaacoub S, Sanad E, Abukhadra A, Elhabyan A, Dinu V |title=The role of host genetics in susceptibility to severe viral infections in humans and insights into host genetics of severe COVID-19: A systematic review |journal=Virus Research |volume=289 |issue= |pages=198163 |date=November 2020 |pmid=32918943 |pmc=7480444 |doi=10.1016/j.virusres.2020.198163 }}</ref>

== Disease mechanisms ==
[[File:Rotavirus infected gut.jpg|thumb|Electron micrograph of a rotavirus infected enterocyte (top) compared to an uninfected cell (bottom). The bar = approx. 500{{nbsp}}nm.|alt=The micrograph at the top shows a damaged cell with a destroyed surface. The micrograph at the bottom shows a healthy cell with its surface intact.]]

Rotaviruses replicate mainly in the gut,<ref name="pmid19457420">{{cite journal |vauthors=Greenberg HB, Estes MK |title=Rotaviruses: from pathogenesis to vaccination |journal=Gastroenterology |volume=136 |issue=6 |pages=1939–1951 |year=2009 |pmid=19457420 |doi=10.1053/j.gastro.2009.02.076 |pmc=3690811 }}</ref> and infect enterocytes of the [[Biology:Intestinal villus|villi]] of the [[Biology:Small intestine|small intestine]], leading to structural and functional changes of the [[Biology:Epithelium|epithelium]].<ref name="pmid8050281">{{cite book |vauthors=Greenberg HB, Clark HF, Offit PA |chapter=Rotavirus Pathology and Pathophysiology |veditors=Ramig RF |series=Current Topics in Microbiology and Immunology|title=Rotaviruses |volume=185 |pages=255–283 |year=1994 |pmid=8050281|publisher=Springer|location=New York|isbn=978-3-540-56761-5|doi=10.1007/978-3-642-78256-5_9 }}</ref> There is evidence in humans, and particularly in animal models of extraintestinal dissemination of infectious virus to other organs and macrophages.<ref name="pmid16641274">{{cite journal |vauthors=Crawford SE, Patel DG, Cheng E, Berkova Z, Hyser JM, Ciarlet M, Finegold MJ, Conner ME, Estes MK |title=Rotavirus viremia and extraintestinal viral infection in the neonatal rat model |journal=Journal of Virology |volume=80 |issue=10 |pages=4820–4832 |year=2006 |pmid=16641274 |pmc=1472071 |doi=10.1128/JVI.80.10.4820-4832.2006 }}</ref>

The diarrhoea is caused by multiple activities of the virus.<ref name="pmid15367586">{{cite journal |vauthors=Ramig RF |title=Pathogenesis of intestinal and systemic rotavirus infection |journal=Journal of Virology |volume=78 |issue=19 |pages=10213–10220 |year=2004 |pmid=15367586 |pmc=516399 |doi=10.1128/JVI.78.19.10213-10220.2004 }}</ref> Malabsorption occurs because of the destruction of gut cells called [[Biology:Enterocyte|enterocyte]]s. The [[Biology:Enterotoxin|toxic]] rotavirus protein NSP4 induces age- and [[Chemistry:Calcium|calcium]] ion-dependent [[Chemistry:Chloride|chloride]] secretion, disrupts [[Biology:Sodium-glucose transport proteins|SGLT1 (sodium/glucose cotransporter 2)]] [[Biology:Membrane transport protein|transporter]]-mediated reabsorption of water, apparently reduces activity of [[Biology:Brush border|brush-border membrane]] [[Biology:Disaccharidase|disaccharidase]]s, and activates the calcium ion-dependent [[Biology:Secretion|secretory]] [[Biology:Reflex|reflex]]es of the [[Biology:Enteric nervous system|enteric nervous system]].<ref name="pmid19114772" /> The elevated concentrations of calcium ions in the cytosol (which are required for the assembly of the progeny viruses) is achieved by NSP4 acting as a [[Biology:Viroporin|viroporin]]. This increase in calcium ions leads to autophagy (self destruction) of the infected enterocytes.<ref name="pmid21151776">{{cite journal |vauthors=Hyser JM, Collinson-Pautz MR, Utama B, Estes MK |title=Rotavirus disrupts calcium homeostasis by NSP4 viroporin activity |journal=mBio   |volume=1 |issue=5 |year=2010 |pmid=21151776 |pmc=2999940 |doi=10.1128/mBio.00265-10 }}</ref>

NSP4 is also secreted. This extracellular form, which is modified by [[Biology:Protease|protease]] enzymes in the gut, is an enterotoxin which acts on uninfected cells via [[Biology:Integrin|integrin]] receptors, which in turn cause and increase in intracellular calcium ion concentrations, secretory diarrhoea and autophagy.<ref name="pmid16731945">{{cite journal |vauthors=Berkova Z, Crawford SE, Trugnan G, Yoshimori T, Morris AP, Estes MK |title=Rotavirus NSP4 induces a novel vesicular compartment regulated by calcium and associated with viroplasms |journal=Journal of Virology |volume=80 |issue=12 |pages=6061–6071 |year=2006 |pmid=16731945 |pmc=1472611 |doi=10.1128/JVI.02167-05 }}</ref>

The vomiting, which is a characteristic of rotaviral enteritis, is caused by the virus infecting the [[Biology:Enterochromaffin cell|enterochromaffin cell]]s on the lining of the digestive tract. The infection stimulates the production of 5' hydroxytryptamine ([[Chemistry:Serotonin|serotonin]]). This activates vagal afferent nerves, which in turn activates the cells of the brain stem that control the vomiting reflex.<ref name="pmid22722079">{{cite journal |vauthors=Hagbom M, Sharma S, Lundgren O, Svensson L |title=Towards a human rotavirus disease model |journal=Current Opinion in Virology |volume=2 |issue=4 |pages=408–418 |year=2012 |pmid=22722079 |doi=10.1016/j.coviro.2012.05.006 }}</ref>

Healthy enterocytes secrete [[Biology:Lactase|lactase]] into the small intestine; milk intolerance due to lactase deficiency is a symptom of rotavirus infection,<ref name="pmid18492865">{{cite journal |author=Farnworth ER |title=The evidence to support health claims for probiotics |journal=The Journal of Nutrition |volume=138 |issue=6 |pages=1250S–1254S |year=2008 |pmid=18492865 |doi=10.1093/jn/138.6.1250S |doi-access=free }}</ref> which can persist for weeks.<ref name="pmid12811680">{{cite journal |vauthors=Ouwehand A, Vesterlund S |title=Health aspects of probiotics |journal=IDrugs: The Investigational Drugs Journal |volume=6 |issue=6 |pages=573–580 |year=2003 |pmid=12811680 }}</ref> A recurrence of mild diarrhoea often follows the reintroduction of milk into the child's diet, due to bacterial fermentation of the [[Chemistry:Disaccharide|disaccharide]] [[Chemistry:Lactose|lactose]] in the gut.<ref name="pmid6436397">{{cite journal
|author=Arya SC
|title=Rotaviral infection and intestinal lactase level
|journal=Journal of Infectious Diseases
|volume=150
|issue=5
|page=791
|year=1984
|pmid=6436397
|doi=10.1093/infdis/150.5.791
|doi-access=free
}}</ref>

== Immune responses ==
=== Specific responses ===
Rotaviruses elicit both B and T cell immune responses. Antibodies to the rotavirus VP4 and VP7 proteins neutralise viral infectivity ''in vitro'' and ''in vivo''.<ref name="pmid19252425">{{cite journal |vauthors=Ward R |title=Mechanisms of protection against rotavirus infection and disease |journal=The Pediatric Infectious Disease Journal |volume=28 |issue=Suppl 3 |pages=S57–S59 |year=2009 |pmid=19252425 |doi=10.1097/INF.0b013e3181967c16 |doi-access=free }}</ref> Specific antibodies of the classes IgM, IgA and IgG are produced, which have been shown to protect against rotavirus infection by the passive transfer of the antibodies in other animals.<ref name="pmid22880110">{{cite journal |vauthors=Vega CG, Bok M, Vlasova AN, Chattha KS, Fernández FM, Wigdorovitz A, Parreño VG, Saif LJ |title=IgY antibodies protect against human Rotavirus induced diarrhea in the neonatal gnotobiotic piglet disease model |journal=PLOS ONE |volume=7 |issue=8 |pages=e42788 |year=2012 |pmid=22880110 |pmc=3411843 |doi=10.1371/journal.pone.0042788 |bibcode=2012PLoSO...742788V |doi-access=free }}</ref> Maternal trans-placental IgG might play a role in the protection neonates from rotavirus infections, but on the other hand might reduce vaccine efficacy.<ref name="pmid27847365">{{cite journal |vauthors=Mwila K, Chilengi R, Simuyandi M, Permar SR, Becker-Dreps S |title=Contribution of Maternal Immunity to Decreased Rotavirus Vaccine Performance in Low- and Middle-Income Countries |journal=Clinical and Vaccine Immunology |volume=24 |issue=1 |year=2017 |pmid=27847365 |pmc=5216432 |doi=10.1128/CVI.00405-16 }}</ref>

=== Innate responses ===
Following infection by rotaviruses there is a rapid innate immune response involving types I and III [[Biology:Interferon|interferon]]s and other [[Biology:Cytokine|cytokine]]s (particularly Th1 and Th2)<ref name="pmid28414969">{{cite journal |vauthors=Gandhi GR, Santos VS, Denadai M, da Silva Calisto VK, de Souza Siqueira Quintans J, de Oliveira e Silva AM, de Souza Araújo AA, Narain N, Cuevas LE, Júnior LJ, Gurgel RQ |s2cid=3568330 |title=Cytokines in the management of rotavirus infection: A systematic review of in vivo studies |journal=Cytokine |volume=96 |pages=152–160 |year=2017 |pmid=28414969 |doi=10.1016/j.cyto.2017.04.013 |url=http://archive.lstmed.ac.uk/7055/2/Cytokine_96_152-160_14.4.17%20Submitted.docx}}</ref> which inhibit the replication of the virus and recruit [[Biology:Macrophage|macrophage]]s and [[Biology:Natural killer cell|natural killer cell]]s to the rotavirus infected cells.<ref name="pmid23486667">{{cite journal |vauthors=Holloway G, Coulson BS |title=Innate cellular responses to rotavirus infection |journal=The Journal of General Virology |volume=94 |issue= 6 |pages=1151–1160 |year=2013 |pmid=23486667 |doi=10.1099/vir.0.051276-0 |doi-access=free }}</ref> The rotavirus dsRNA activates pattern recognition receptors such [[Biology:Toll-like receptor|toll-like receptor]]s that stimulate the production of interferons.<ref name="pmid27994593" /> The rotavirus protein NSP1 counteracts the effects of type 1 interferons by suppressing the activity of the interferon regulatory proteins IRF3, IRF5 and IRF7.<ref name="pmid27994593">{{cite journal |vauthors=Villena J, Vizoso-Pinto MG, Kitazawa H |title=Intestinal Innate Antiviral Immunity and Immunobiotics: Beneficial Effects against Rotavirus Infection |journal=Frontiers in Immunology |volume=7 |pages=563 |year=2016 |pmid=27994593 |pmc=5136547 |doi=10.3389/fimmu.2016.00563 |doi-access=free }}</ref>

=== Markers of protection ===
The levels of IgG and IgA in the blood and IgA in the gut correlate with protection from infection.<ref name="pmid7817873">{{cite journal |vauthors=Offit PA |title=Rotaviruses: immunological determinants of protection against infection and disease |journal=Advances in Virus Research |volume=44 |issue= |pages=161–202 |date=1994 |pmid=7817873 |pmc=7130874 |doi=10.1016/s0065-3527(08)60329-2 |isbn=9780120398447 }}</ref> Rotavirus specific serum IgG and IgA at high titres (e.g. >1:200) have been claimed to be protective and there is a significant correlation between IgA titres and rotavirus vaccine efficacy.<ref name="pmid23596320">{{cite journal |vauthors=Patel M, Glass RI, Jiang B, Santosham M, Lopman B, Parashar U |title=A systematic review of anti-rotavirus serum IgA antibody titer as a potential correlate of rotavirus vaccine efficacy |journal=The Journal of Infectious Diseases |volume=208 |issue=2 |pages=284–294 |year=2013 |pmid=23596320 |doi=10.1093/infdis/jit166 |doi-access=free }}</ref>

== Diagnosis and detection ==
Diagnosis of infection with a rotavirus normally follows diagnosis of [[Medicine:Gastroenteritis|gastroenteritis]] as the cause of severe diarrhoea. Most children admitted to hospital with gastroenteritis are tested for rotavirus.<ref name="pmid17901797" /><ref name="pmid16650331">{{cite journal |author=The Pediatric ROTavirus European CommitTee (PROTECT) |title=The paediatric burden of rotavirus disease in Europe |journal=Epidemiology and Infection |volume=134 |issue=5 |pages=908–916 |year=2006 |pmid=16650331 |pmc=2870494 |doi=10.1017/S0950268806006091}}</ref>

Specific [[Medicine:Medical diagnosis|diagnosis]] of infection with rotavirus is made by finding the virus in the child's [[Medicine:Human feces|stool]] by enzyme immunoassay. There are several licensed test kits on the market which are sensitive, specific and detect all serotypes of rotavirus.<ref name="isbn0-12-375147-0">{{cite book |vauthors=Angel J, Franco MA, Greenberg HB |veditors=Mahy WJ, Van Regenmortel MH  |title=Desk Encyclopedia of Human and Medical Virology|publisher=Academic Press |location=Boston |year=2009|page=278|isbn=978-0-12-375147-8}}</ref> Other methods, such as [[Physics:Electron microscopy|electron microscopy]] and [[Biology:Polymerase chain reaction|PCR]] (polymerase chain reaction), are used in research laboratories.<ref name="isbn0-471-49663-4">{{cite book |vauthors=Goode J, Chadwick D |title=Gastroenteritis viruses |publisher=Wiley |location=New York |year=2001 |page=14 |isbn=978-0-471-49663-2}}</ref> Reverse transcription-polymerase chain reaction (RT-PCR) can detect and identify all species and serotypes of human rotaviruses.<ref name="pmid15027000">{{cite journal |vauthors=Fischer TK, Gentsch JR |title=Rotavirus typing methods and algorithms |journal=Reviews in Medical Virology |volume=14 |issue=2 |pages=71–82 |year=2004 |pmid=15027000 |doi=10.1002/rmv.411|url=https://zenodo.org/record/1229353 |pmc=7169166 }}</ref>

== Treatment and prognosis ==
Treatment of acute rotavirus infection is nonspecific and involves management of symptoms and, most importantly, management of dehydration.<ref name="pmid18026034">{{cite journal|author=Diggle L|title=Rotavirus diarrhea and future prospects for prevention|journal=British Journal of Nursing|volume=16|issue=16|pages=970–974|year=2007|pmid=18026034|doi=10.12968/bjon.2007.16.16.27074}}</ref> If untreated, children can die from the resulting severe dehydration.<ref name="pmid12608880">{{cite journal|vauthors=Alam NH, Ashraf H |s2cid=26076784|title=Treatment of infectious diarrhea in children|journal=Paediatric Drugs|volume=5|issue=3|pages=151–165|year=2003|pmid=12608880|doi=10.2165/00128072-200305030-00002|doi-access=free}}</ref> Depending on the severity of diarrhoea, treatment consists of [[Medicine:Oral rehydration therapy|oral rehydration therapy]], during which the child is given extra water to drink that contains specific amounts of salt and sugar.<ref name="pmid8855579">{{cite journal |author=Sachdev HP |title=Oral rehydration therapy |journal=Journal of the Indian Medical Association |volume=94 |issue=8 |pages=298–305 |year=1996 |pmid=8855579}}</ref> In 2004, the World Health Organisation (WHO) and UNICEF recommended the use of low-osmolarity [[Medicine:Oral rehydration therapy|oral rehydration solution]] and [[Chemistry:Zinc|zinc]] supplementation as a two-pronged treatment of acute diarrhoea.<ref name="WHO UNICEF">{{cite web|author=World Health Organization, UNICEF|title=Joint Statement: Clinical Management of Acute Diarrhoea|url=http://whqlibdoc.who.int/hq/2004/WHO_FCH_CAH_04.7.pdf|access-date=3 May 2012}}</ref> Some infections are serious enough to warrant hospitalisation where fluids are given by [[Chemistry:Intravenous therapy|intravenous therapy]] or [[Medicine:Nasogastric intubation|nasogastric intubation]], and the child's [[Physics:Electrolyte|electrolyte]]s and blood sugar are monitored.<ref name="pmid17901797">{{cite journal |vauthors=Patel MM, Tate JE, Selvarangan R, Daskalaki I, Jackson MA, Curns AT, Coffin S, Watson B, Hodinka R, Glass RI, Parashar UD |s2cid=10992309 |title=Routine laboratory testing data for surveillance of rotavirus hospitalizations to evaluate the impact of vaccination |journal=The Pediatric Infectious Disease Journal |volume=26 |issue=10 |pages=914–919 |year= 2007 |pmid=17901797 |doi=10.1097/INF.0b013e31812e52fd}}</ref> Rotavirus infections rarely cause other complications and for a well managed child the prognosis is excellent.<ref name="pmid17678424">{{cite journal |author=Ramig RF |s2cid=27763488 |title=Systemic rotavirus infection |journal=Expert Review of Anti-infective Therapy |volume=5 |issue=4 |pages=591–612 |date=2007 |pmid=17678424 |doi=10.1586/14787210.5.4.591}}</ref> [[Biology:Probiotic|Probiotic]]s have been shown to reduce the duration of rotavirus diarrhoea,<ref name="pmid26644891">{{cite journal |vauthors=Ahmadi E, Alizadeh-Navaei R, Rezai MS |title=Efficacy of probiotic use in acute rotavirus diarrhea in children: A systematic review and meta-analysis |journal=Caspian Journal of Internal Medicine |volume=6 |issue=4 |pages=187–195 |year=2015 |pmid=26644891 |pmc=4649266 }}</ref> and according to the European Society for Pediatric Gastroenterology "effective interventions include administration of specific probiotics such as ''[[Biology:Lactobacillus rhamnosus|Lactobacillus rhamnosus]]'' or ''[[Biology:Saccharomyces boulardii|Saccharomyces boulardii]]'', [[Chemistry:Diosmectite|diosmectite]] or [[Chemistry:Racecadotril|racecadotril]]."<ref name="pmid24739189">{{cite journal |vauthors=Guarino A, Ashkenazi S, Gendrel D, Lo Vecchio A, Shamir R, Szajewska H |title=European Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Society for Pediatric Infectious Diseases evidence-based guidelines for the management of acute gastroenteritis in children in Europe: update 2014 |journal=Journal of Pediatric Gastroenterology and Nutrition |volume=59 |issue=1 |pages=132–152 |year=2014 |pmid=24739189 |doi=10.1097/MPG.0000000000000375 |s2cid=4845135 |doi-access=free }}</ref>

== Prevention ==
{{Main|Medicine:Rotavirus vaccine}}
Rotaviruses are highly contagious and cannot be treated with antibiotics or other drugs. Because improved [[Engineering:Sanitation|sanitation]] does not decrease the prevalence of rotaviral disease, and the rate of hospitalisations remains high despite the use of oral rehydrating medicines, the primary public health intervention is vaccination.<ref name="pmid19252423">{{cite journal |author=Bernstein DI |title=Rotavirus overview |journal=The Pediatric Infectious Disease Journal |volume=28 |issue= Suppl 3|pages=S50–S53 |year= 2009 |pmid=19252423 |doi=10.1097/INF.0b013e3181967bee |s2cid=30544613 |doi-access=free }}</ref> In 1998, a [[Medicine:Rotavirus vaccine|rotavirus vaccine]] was licensed for use in the United States. Clinical trials in the United States, Finland, and Venezuela had found it to be 80–100% effective at preventing severe diarrhoea caused by ''rotavirus A'', and researchers had detected no [[Statistical significance|statistically significant]] serious [[Medicine:Adverse drug reaction|adverse effects]].<ref name="pmid10219046">{{cite journal |title=Rotavirus vaccine for the prevention of rotavirus gastroenteritis among children. Recommendations of the Advisory Committee on Immunization Practices (ACIP) |journal=MMWR. Recommendations and Reports |volume=48 |issue=RR-2 |pages=1–20 |year=1999 |pmid=10219046 }}</ref><ref name="pmid11444025">{{cite book
|author=Kapikian AZ
|title=Gastroenteritis Viruses
|chapter=A rotavirus vaccine for prevention of severe diarrhoea of infants and young children: development, utilization and withdrawal
|volume=238
|pages=153–171; discussion 171–179
|year=2001
|pmid=11444025
|doi=10.1002/0470846534.ch10
|series=Novartis Foundation Symposia
|isbn=978-0-470-84653-7
}}</ref> The manufacturer, however, withdrew it from the market in 1999, after it was discovered that the vaccine may have contributed to an increased risk for [[Medicine:Intussusception (medical disorder)|intussusception]], a type of [[Medicine:Bowel obstruction|bowel obstruction]], in one of every 12,000 vaccinated infants.<ref name="pmid15687880">{{cite journal |author=Bines |first=JE |year=2005 |title=Rotavirus vaccines and intussusception risk |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0267-1379&volume=21&issue=1&spage=20 |journal=Current Opinion in Gastroenterology |volume=21 |issue=1 |pages=20–25 |pmid=15687880 |access-date=21 January 2008 |archive-date=11 May 2013 |archive-url=https://web.archive.org/web/20130511014221/http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0267-1379&volume=21&issue=1&spage=20 |url-status=dead }}</ref> The experience provoked intense debate about the relative risks and benefits of a rotavirus vaccine.<ref name="pmid16099078">{{cite journal |author=Bines J |title=Intussusception and rotavirus vaccines |journal=Vaccine |volume=24 |issue=18 |pages=3772–3776 |year=2006 |pmid=16099078 |doi=10.1016/j.vaccine.2005.07.031}}</ref>

In 2006, two new vaccines against ''{{nowrap|rotavirus A}}'' infection were shown to be safe and effective in children,<ref name="pmid18202442">{{cite journal
|author=Dennehy PH
|title=Rotavirus vaccines: an overview
|journal=Clinical Microbiology Reviews
|volume=21
|issue=1
|pages=198–208
|year=2008
|pmid=18202442
|doi=10.1128/CMR.00029-07
|pmc=2223838
}}</ref> and in 2009, the WHO recommended that rotavirus vaccine be included in all national immunisation programmes.<ref name="pmid20370550">{{cite journal |vauthors=Tate JE, Patel MM, Steele AD, Gentsch JR, Payne DC, Cortese MM, Nakagomi O, Cunliffe NA, Jiang B, Neuzil KM, de Oliveira LH, Glass RI, Parashar UD |s2cid=28963507 |title=Global impact of rotavirus vaccines |journal=Expert Review of Vaccines |volume=9 |issue=4 |pages=395–407 |year= 2010 |pmid=20370550 |doi=10.1586/erv.10.17}}</ref>

The incidence and severity of rotavirus infections has declined significantly in countries that have acted on this recommendation.<ref name="pmid21734466">{{cite journal |vauthors=Giaquinto C, Dominiak-Felden G, Van Damme P, Myint TT, Maldonado YA, Spoulou V, Mast TC, Staat MA |s2cid=23996836 |title=Summary of effectiveness and impact of rotavirus vaccination with the oral pentavalent rotavirus vaccine: a systematic review of the experience in industrialized countries |journal=Human Vaccines |volume=7 |issue=7 |pages=734–748 |year =2011 |pmid=21734466 |doi=10.4161/hv.7.7.15511 |url=http://www.landesbioscience.com/journals/hv/abstract.php?id=15511|doi-access=free }}</ref><ref name="pmid20622508" /><ref name=":2" /> A 2014 review of available clinical trial data from countries routinely using rotavirus vaccines in their national immunisation programs found that rotavirus vaccines have reduced rotavirus hospitalisations by 49–92% and all cause diarrhoea hospitalisations by 17–55%.<ref>{{Cite journal|vauthors=Tate JE, Parashar UD|date=2014|title=Rotavirus Vaccines in Routine Use|journal=Clinical Infectious Diseases|volume=59|issue=9|pages=1291–1301|doi=10.1093/cid/ciu564|pmid=25048849|doi-access=free}}</ref> In Mexico, which in 2006 was among the first countries in the world to introduce rotavirus vaccine, diarrhoeal disease death rates dropped during the 2009 rotavirus season by more than 65 percent among children age two and under.<ref>{{cite journal|vauthors=Richardson V, Hernandez-Pichardo J, Quintanar-Solares M, Esparza-Aguilar M, Johnson B, Gomez-Altamirano CM, Parashar U, Patel M |s2cid=27287753|title=Effect of Rotavirus Vaccination on Death From Childhood Diarrhea in Mexico|journal=The New England Journal of Medicine|year=2010|volume=362|issue=4|pages=299–305|doi=10.1056/NEJMoa0905211|pmid=20107215|display-authors=2|doi-access=free}}</ref> In Nicaragua, which in 2006 became the first developing country to introduce a rotavirus vaccine, severe rotavirus infections were reduced by 40 percent and emergency room visits by a half.<ref name="pmid22753550">{{cite journal |vauthors=Patel M, Pedreira C, De Oliveira LH, Umaña J, Tate J, Lopman B, Sanchez E, Reyes M, Mercado J, Gonzalez A, Perez MC, Balmaceda A, Andrus J, Parashar U |s2cid=7723807 |title=Duration of protection of pentavalent rotavirus vaccination in Nicaragua |journal=Pediatrics |volume=130 |issue=2 |pages=e365–e372 |year=2012 |pmid=22753550 |doi=10.1542/peds.2011-3478 }}</ref> In the United States, rotavirus vaccination since 2006 has led to drops in rotavirus-related hospitalisations by as much as 86 percent.<ref name="pmid35632617">{{cite journal |vauthors=Omatola CA, Olaniran AO |title=Rotaviruses: From Pathogenesis to Disease Control-A Critical Review |journal=Viruses |volume=14 |issue=5 |date=April 2022 |page=875 |pmid=35632617 |pmc=9143449 |doi=10.3390/v14050875|doi-access=free }}</ref> The vaccines may also have prevented illness in non-vaccinated children by limiting the number of circulating infections.<ref name="pmid35632617" /><ref>{{cite journal|vauthors=Patel MM, Parashar UD, etal |title=Real World Impact of Rotavirus Vaccination|journal=Pediatric Infectious Disease Journal|year=2011|volume=30|issue=1|doi=10.1097/INF.0b013e3181fefa1f|pages=S1–S5|pmid=21183833|s2cid=1893099 |doi-access=free}}</ref> In developing countries in Africa and Asia, where the majority of rotavirus deaths occur, a large number of safety and efficacy trials as well as recent post-introduction impact and effectiveness studies of Rotarix and RotaTeq have found that vaccines dramatically reduced severe disease among infants.<ref name=":2" /><ref>{{Cite journal|date=2010|veditors=Steele AD, Armah GE, Page NA, Cunliffe NA|title=Rotavirus Infection in Africa: Epidemiology, Burden of Disease, and Strain Diversity|journal=Journal of Infectious Diseases|volume=202|issue=Suppl 1|pages=S1–S265|doi=10.1086/653545|pmid=20684687|vauthors=Neuzil KM, Armah GE, Parashar UD, Steele AD |doi-access=free}}</ref><ref>{{Cite journal|date=2009|veditors=Nelson EA, Widdowson MA, Kilgore PE, Steele D, Parashar UD|title=Rotavirus in Asia: Updates on Disease Burden, Genotypes and Vaccine Introduction|url=http://www.sciencedirect.com/science/journal/0264410X/27/supp/S5|journal=Vaccine|volume=27|issue=Suppl 5|pages=F1–F138}}</ref><ref>{{cite journal|author=World Health Organization|title=Rotavirus vaccines: an update|journal=Weekly Epidemiological Record|year= 2009|volume=51–52|issue=84|pages=533–540|url=https://www.who.int/wer/2009/wer8451_52.pdf|access-date=8 May 2012}}</ref> In September 2013, the vaccine was offered to all children in the UK, aged between two and three months, and it is expected to halve the cases of severe infection and reduce the number of children admitted to hospital because of the infection by 70 percent.<ref>{{cite web|url=http://www.dh.gov.uk/health/2012/11/rotavirus/ |title= New vaccine to help protect babies against rotavirus|publisher=UK Department of Health|date=10 November 2012 |access-date= 10 November 2012}}</ref> In Europe, hospitalisation rates following infection by rotaviruses have decreased by 65% to 84% following the introduction of the vaccine.<ref name="pmid25795258">{{cite journal |vauthors=Karafillakis E, Hassounah S, Atchison C |title=Effectiveness and impact of rotavirus vaccines in Europe, 2006–2014 |journal=Vaccine |volume=33 |issue=18 |pages=2097–2107 |year=2015 |pmid=25795258 |doi=10.1016/j.vaccine.2015.03.016 |doi-access=free }}</ref> Globally, vaccination has reduced hospital admissions and emergency department visits by a median of 67%.<ref name="pmid28430997">{{cite journal |vauthors=Burnett E, Jonesteller CL, Tate JE, Yen C, Parashar UD |title=Global Impact of Rotavirus Vaccination on Childhood Hospitalizations and Mortality from Diarrhea |journal=The Journal of Infectious Diseases |volume=215 |issue=11 |pages=1666–1672 |year=2017 |pmid=28430997 |doi=10.1093/infdis/jix186 |pmc=5543929}}</ref>

Rotavirus vaccines are licensed in over 100 countries, and more than 80 countries have introduced routine rotavirus vaccination, almost half with the support of the [[Organization:GAVI|GAVI]] vaccine alliance.<ref>{{Cite web|url=http://rotacouncil.org/toolkit/rotavirus-burden-vaccine-introduction-map/|title=Rotavirus Deaths & Rotavirus Vaccine Introduction Maps – ROTA Council|website=rotacouncil.org|access-date=29 July 2016|archive-url=https://web.archive.org/web/20160712033209/http://rotacouncil.org/toolkit/rotavirus-burden-vaccine-introduction-map/|archive-date=12 July 2016}}</ref> To make rotavirus vaccines available, accessible, and affordable in all countries—particularly low- and middle-income countries in Africa and Asia where the majority of rotavirus deaths occur, [[Organization:PATH (global health organization)|PATH]] (formerly Program for Appropriate Technology in Health), the WHO, the U.S. Centers for Disease Control and Prevention, and GAVI have partnered with research institutions and governments to generate and disseminate evidence, lower prices, and accelerate introduction.<ref name="pmid21957215">{{cite journal |author=Moszynski P |s2cid=7567316 |title=GAVI rolls out vaccines against child killers to more countries |journal=BMJ |volume=343 |pages=d6217 |year=2011 |pmid=21957215 |doi=10.1136/bmj.d6217 }}</ref>

The vaccine may prevent [[Medicine:Diabetes mellitus type 1|type 1 diabetes]].<ref>{{Cite news|url=https://www.reuters.com/article/us-health-diabetes-rotavirus-idUSKCN1PG2L8|title=Rotavirus vaccination tied to lower rates of type 1 diabetes|date=2019-01-22|work=Reuters|access-date=2019-02-10}}</ref><ref>{{Cite news|url=https://www.nytimes.com/2019/01/30/well/live/rotavirus-vaccine-may-protect-against-type-1-diabetes.html|title=Rotavirus Vaccine May Protect Against Type 1 Diabetes|last=Bakalar|first=Nicholas|date=2019-01-30|work=The New York Times|access-date=2019-02-10|issn=0362-4331}}</ref>

== Epidemiology ==
''Rotavirus A'', which accounts for more than 90% of rotavirus gastroenteritis in humans,<ref name="pmid16418157">{{cite journal |vauthors=Leung AK, Kellner JD, Davies HD |s2cid=39847059 |title=Rotavirus gastroenteritis |journal=Advances in Therapy |volume=22 |issue=5 |pages=476–487 |year=2005 |pmid=16418157 |doi=10.1007/BF02849868 }}</ref> is [[Medicine:Endemic (epidemiology)|endemic]] worldwide. Each year rotaviruses cause millions of cases of diarrhoea in developing countries, almost 2{{nbsp}}million of which result in hospitalisation.<ref name="pmid17919334" /> In 2019, an estimated 151,714 children younger than five died from rotavirus infections, 90 percent of whom were in developing countries.<ref name="pmid35643565" /> Almost every child has been infected with rotaviruses by age five.<ref name="pmid16494759">{{cite journal
|vauthors=Parashar UD, Gibson CJ, Bresse JS, Glass RI |title=Rotavirus and severe childhood diarrhea
|journal=Emerging Infectious Diseases
|volume=12
|issue=2
|pages=304–306
|year=2006
|pmid=16494759
|doi=10.3201/eid1202.050006
|pmc=3373114
}}</ref> Rotaviruses are the leading single cause of severe diarrhoea among infants and children, is responsible for about a third of the cases requiring hospitalisation,<ref name=":1" /> and causes 37% of deaths attributable to diarrhoea and 5% of all deaths in children younger than five.<ref name="pmid22030330">{{cite journal|year= 2012|title=2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis|journal=The Lancet Infectious Diseases|volume=12|issue=2|pages=136–141|doi=10.1016/S1473-3099(11)70253-5|pmid=22030330|vauthors=Tate JE, Burton AH, Boschi-Pinto C, Steele AD, Duque J, Parashar UD|url=https://zenodo.org/record/1260248}}</ref> Boys are twice as likely as girls to be admitted to hospital for rotavirus infections.<ref name="pmid16397429">{{cite journal |vauthors=Rheingans RD, Heylen J, Giaquinto C |s2cid=3272810 |title=Economics of rotavirus gastroenteritis and vaccination in Europe: what makes sense? |journal=Pediatric Infectious Disease Journal |volume=25 |issue= Suppl 1|pages=S48–S55 |year=2006 |pmid=16397429 |doi=10.1097/01.inf.0000197566.47750.3d|doi-access=free }}</ref><ref name="pmid8752285">{{cite journal |vauthors=Ryan MJ, Ramsay M, Brown D, Gay NJ, Farrington CP, Wall PG |title=Hospital admissions attributable to rotavirus infection in England and Wales |journal=Journal of Infectious Diseases |volume=174 |issue=Suppl 1 |pages=S12–S18 |year=1996 |pmid=8752285 |doi=10.1093/infdis/174.Supplement_1.S12|doi-access=free }}</ref> In the pre-vaccination era, rotavirus infections occurred primarily during cool, dry seasons.<ref name="pmid19939844">{{cite journal |vauthors=Atchison CJ, Tam CC, Hajat S, van Pelt W, Cowden JM, Lopman BA |title=Temperature-dependent transmission of rotavirus in Great Britain and The Netherlands |journal=Proceedings of the Royal Society B: Biological Sciences |volume=277 |issue=1683 |pages=933–942 |year=2010 |pmid=19939844 |pmc=2842727 |doi=10.1098/rspb.2009.1755}}</ref><ref name="pmid19056806">{{cite journal |vauthors=Levy K, Hubbard AE, Eisenberg JN |title=Seasonality of rotavirus disease in the tropics: a systematic review and meta-analysis |journal=International Journal of Epidemiology |volume=38 |issue=6 |pages=1487–1496 |year= 2009 |pmid=19056806 |pmc=2800782 |doi=10.1093/ije/dyn260 }}</ref> The number attributable to food contamination is unknown.<ref name="pmid10088906">{{cite journal |vauthors=Koopmans M, Brown D |title=Seasonality and diversity of Group A rotaviruses in Europe |journal=Acta Paediatrica  |volume=88 |issue=Suppl 426 |pages=14–19 |year=1999 |pmid=10088906 |doi=10.1111/j.1651-2227.1999.tb14320.x|s2cid=10969637 }}</ref>

Outbreaks of ''rotavirus A'' diarrhoea are common among hospitalised infants, young children attending day care centres, and elderly people in nursing homes.<ref name="pmid14871633" /><ref name="pmid25944726">{{cite journal |vauthors=Sassi HP, Sifuentes LY, Koenig DW, Nichols E, Clark-Greuel J, Wong LF, McGrath K, Gerba CP, Reynolds KA |title=Control of the spread of viruses in a long-term care facility using hygiene protocols |journal=American Journal of Infection Control |volume=43 |issue=7 |pages=702–706 |year=2015 |pmid=25944726 |doi=10.1016/j.ajic.2015.03.012 |doi-access=free }}</ref> An outbreak caused by contaminated municipal water occurred in Colorado in 1981.<ref name="pmid6320684">{{cite journal |vauthors=Hopkins RS, Gaspard GB, Williams FP, Karlin RJ, Cukor G, Blacklow NR |title=A community waterborne gastroenteritis outbreak: evidence for rotavirus as the agent |journal=American Journal of Public Health |volume=74 |issue=3 |pages=263–265 |year=1984 |pmid=6320684 |pmc=1651463 |doi=10.2105/AJPH.74.3.263}}</ref> During 2005, the largest recorded epidemic of diarrhoea occurred in Nicaragua. This unusually large and severe outbreak was associated with mutations in the ''rotavirus A'' genome, possibly helping the virus escape the prevalent immunity in the population.<ref name="pmid17229854">{{cite journal  |vauthors=Bucardo F, Karlsson B, Nordgren J, Paniagua M, González A, Amador JJ, Espinoza F, Svensson L|title=Mutated G4P&#91;8&#93; rotavirus associated with a nationwide outbreak of gastroenteritis in Nicaragua in 2005 |journal=Journal of Clinical Microbiology |volume=45 |issue=3 |pages=990–997 |year=2007 |pmid=17229854 |doi=10.1128/JCM.01992-06 |pmc=1829148}}</ref> A similar large outbreak occurred in Brazil in 1977.<ref name="pmid6263087">{{cite journal |vauthors=Linhares AC, Pinheiro FP, Freitas RB, Gabbay YB, Shirley JA, Beards GM |title=An outbreak of rotavirus diarrhea among a non-immune, isolated South American Indian community |journal=American Journal of Epidemiology |volume=113 |issue=6 |pages=703–710 |year=1981 |pmid=6263087|doi=10.1093/oxfordjournals.aje.a113151}}</ref>

''Rotavirus B'', also called adult diarrhoea rotavirus or ADRV, has caused major epidemics of severe diarrhoea affecting thousands of people of all ages in China. These epidemics occurred as a result of sewage contamination of drinking water.<ref name="pmid6144874">{{cite journal  |vauthors=Hung T, Wang C, Fang Z, Chou Z, Chang X, Liong X, Chen G, Yao H, Chao T, Ye W, Den S, Chang W |title=Waterborne outbreak of rotavirus diarrhea in adults in China caused by a novel rotavirus |journal=The Lancet |volume=323 |issue=8387 |pages=1139–1142 |year=1984 |pmid=6144874 | doi = 10.1016/S0140-6736(84)91391-6|s2cid=54346351 }}</ref><ref name="pmid2555422">{{cite journal  |vauthors=Fang ZY, Ye Q, Ho MS, Dong H, Qing S, Penaranda ME, Hung T, Wen L, Glass RI |title=Investigation of an outbreak of adult diarrhea rotavirus in China |journal=Journal of Infectious Diseases |volume=160 |issue=6 |pages=948–953 |year=1989 |pmid=2555422 |doi=10.1093/infdis/160.6.948}}</ref> ''Rotavirus B'' infections also occurred in India in 1998; the causative strain was named CAL. Unlike ADRV, the CAL strain is endemic.<ref name="pmid15310177">{{cite journal |vauthors=Kelkar SD, Zade JK |title=Group B rotaviruses similar to strain CAL-1, have been circulating in Western India since 1993 |journal=Epidemiology and Infection |volume=132 |issue=4 |pages=745–749 |year=2004 |pmid=15310177 |pmc=2870156 |doi=10.1017/S0950268804002171}}</ref><ref>{{cite journal |vauthors=Ahmed MU, Kobayashi N, Wakuda M, Sanekata T, Taniguchi K, Kader A, Naik TN, Ishino M, Alam MM, Kojima K, Mise K, Sumi A |title=Genetic analysis of group B human rotaviruses detected in Bangladesh in 2000 and 2001 |journal=Journal of Medical Virology |volume=72 |issue=1 |pages=149–155 |year=2004 |pmid=14635024 |doi=10.1002/jmv.10546|s2cid=21258083 }}</ref> To date, epidemics caused by ''rotavirus B'' have been confined to mainland China, and surveys indicate a lack of immunity to this species in the United States.<ref name="pmid2479654">{{cite journal |vauthors=Penaranda ME, Ho MS, Fang ZY, Dong H, Bai XS, Duan SC, Ye WW, Estes MK, Echeverria P, Hung T |title=Seroepidemiology of adult diarrhea rotavirus in China, 1977 to 1987 |journal=Journal of Clinical Microbiology |volume=27 |issue=10 |pages=2180–2183 |year=1989 |pmid=2479654 |pmc=266989 |doi= 10.1128/JCM.27.10.2180-2183.1989}}</ref> ''Rotavirus C'' has been associated with rare and sporadic cases of diarrhoea in children, and small outbreaks have occurred in families.<ref name="pmid20491826">{{cite journal |vauthors=Moon S, Humphrey CD, Kim JS, Baek LJ, Song JW, Song KJ, Jiang B |title=First detection of group C rotavirus in children with acute gastroenteritis in South Korea |journal=Clinical Microbiology and Infection |volume=17 |issue=2 |pages=244–247 |year=2011 |pmid=20491826 |doi=10.1111/j.1469-0691.2010.03270.x |doi-access=free }}</ref>

<gallery widths="650px" heights="580px">
File:Rotavirus seasonal distribution.png|The seasonal variation of ''rotavirus A'' infections in England: rates of infection peak during the winter months.<ref>{{Cite web|url=https://www.gov.uk/government/collections/rotavirus-vaccination-progarmme-for-infants|title=Rotavirus vaccination programme for infants|website=www.gov.uk|publisher=Public Health England|date=26 July 2013}}</ref>
File:Avertable-deaths-from-rotavirus-with-full-vaccine-coverage.png|Preventable child deaths from rotavirus vaccination, 2016. Annual number of preventable deaths in children under five years old from rotavirus if full coverage of the rotavirus vaccine was achieved.<ref>{{cite journal|url=https://ourworldindata.org/rotavirus-vaccine|title=Rotavirus vaccine – an effective tool that prevents children dying from diarrhea|vauthors=Dadonaite B, Ritchie H|journal=Our World in Data |year=2019}}</ref>
</gallery>

== Other animals ==
Rotaviruses infect the young of many species of animals and they are a major cause of diarrhoea in wild and reared animals worldwide.<ref name="isbn0-12-375158-6">{{cite book |vauthors=Dubovi EJ, MacLachlan NJ |title=Fenner's Veterinary Virology|edition=4th |publisher=Academic Press |location=Boston |year=2010 |page=288 |isbn=978-0-12-375158-4}}</ref> As a pathogen of livestock, notably in young calves and piglets, rotaviruses cause  economic loss to farmers because of costs of treatment associated with high morbidity and mortality rates.<ref name="pmid19781872">{{cite journal |vauthors=Martella V, Bányai K, Matthijnssens J, Buonavoglia C, Ciarlet M |title=Zoonotic aspects of rotaviruses |journal=Veterinary Microbiology |volume=140 |issue=3–4 |pages=246–255 |year =2010 |pmid=19781872 |doi=10.1016/j.vetmic.2009.08.028|url=https://hal.archives-ouvertes.fr/hal-00556058/document }}</ref> These rotaviruses are a potential reservoir for genetic exchange with human rotaviruses.<ref name="pmid19781872" /> There is evidence that animal rotaviruses can infect humans, either by direct transmission of the virus or by contributing one or several RNA segments to [[Biology:Reassortment|reassortants]] with human strains.<ref name="pmid17416132">{{cite journal |vauthors=Müller H, Johne R |title=Rotaviruses: diversity and zoonotic potential—a brief review |journal=Berliner und Munchener Tierarztliche Wochenschrift |volume=120 |issue=3–4 |pages=108–112 |year=2007 |pmid=17416132 }}</ref><ref name="pmid15066329">{{cite journal |vauthors=Cook N, Bridger J, Kendall K, Gomara MI, El-Attar L, Gray J |title=The zoonotic potential of rotavirus |journal=The Journal of Infection |volume=48 |issue=4 |pages=289–302 |year=2004 |pmid=15066329 |doi=10.1016/j.jinf.2004.01.018 |url=http://researchonline.rvc.ac.uk/id/eprint/1175/ }}</ref><ref name="pmid26428261">{{cite journal |vauthors=Dóró R, Farkas SL, Martella V, Bányai K |s2cid=42693014 |title=Zoonotic transmission of rotavirus: surveillance and control |journal=Expert Review of Anti-infective Therapy |volume=13 |issue=11 |pages=1337–1350 |year=2015 |pmid=26428261 |doi=10.1586/14787210.2015.1089171 }}</ref>

== History ==
[[File:Flewett Rotavirus.jpg|thumb|upright|One of Flewett's original electron micrographs showing a single rotavirus particle. When examined by negative stained electron microscopy, rotaviruses often resemble wheels.]]

In 1943, Jacob Light and Horace Hodes proved that a filterable agent in the faeces of children with infectious diarrhoea also caused scours (livestock diarrhoea) in cattle.<ref name="pmid18015921">{{cite journal |vauthors=Light JS, Hodes HL |title=Studies on Epidemic Diarrhea of the New-born: Isolation of a Filtrable Agent Causing Diarrhea in Calves |journal=American Journal of Public Health and the Nation's Health |volume=33 |issue=12 |pages=1451–1454 |year=1943 |pmid=18015921 |pmc=1527675 |doi=10.2105/AJPH.33.12.1451 }}</ref> Three decades later, preserved samples of the agent were shown to be rotavirus.<ref name="pmid184047">{{cite journal |vauthors=Mebus CA, Wyatt RG, Sharpee RL, Sereno MM, Kalica AR, Kapikian AZ, Twiehaus MJ |title=Diarrhea in gnotobiotic calves caused by the reovirus-like agent of human infantile gastroenteritis |journal=Infection and Immunity |volume=14 |issue=2 |pages=471–474 |year= 1976|doi=10.1128/IAI.14.2.471-474.1976 |pmid=184047 |url=http://iai.asm.org/cgi/reprint/14/2/471 |format=PDF |pmc=420908}}</ref> In the intervening years, a virus in mice<ref name="pmid4998842">{{cite journal |vauthors=Rubenstein D, Milne RG, Buckland R, Tyrrell DA |title=The growth of the virus of epidemic diarrhoea of infant mice (EDIM) in organ cultures of intestinal epithelium |journal=British Journal of Experimental Pathology |volume=52 |issue=4 |pages=442–445 |year=1971 |pmid=4998842 |pmc=2072337}}</ref> was shown to be related to the virus causing scours.<ref name="pmid965097">{{cite journal |vauthors=Woode GN, Bridger JC, Jones JM, Flewett TH, Davies HA, Davis HA, White GB |title=Morphological and antigenic relationships between viruses (rotaviruses) from acute gastroenteritis in children, calves, piglets, mice, and foals |journal=Infection and Immunity |volume=14 |issue=3 |pages=804–810 |year =1976|doi=10.1128/IAI.14.3.804-810.1976 |pmid=965097 |url=http://iai.asm.org/cgi/reprint/14/3/804 |format=PDF |pmc=420956}}</ref> In 1973, Ruth Bishop and colleagues described related viruses found in children with gastroenteritis.<ref name="pmid19799704">{{cite journal |author=Bishop R |title=Discovery of rotavirus: Implications for child health |journal=Journal of Gastroenterology and Hepatology |volume=24 |issue=Suppl 3 |pages=S81–S85 |year =2009 |pmid=19799704 |doi=10.1111/j.1440-1746.2009.06076.x |doi-access=free }}</ref>

In 1974, [[Biography:Thomas Henry Flewett|Thomas Henry Flewett]] suggested the name ''rotavirus'' after observing that, when viewed through an [[Engineering:Electron microscope|electron microscope]], a rotavirus particle looks like a wheel ({{lang|la|rota}} in Latin)<ref name="pmid77663" /><ref name="pmid4137164">{{cite journal |vauthors=Flewett TH, Bryden AS, Davies H, Woode GN, Bridger JC, Derrick JM |title=Relation between viruses from acute gastroenteritis of children and newborn calves |journal=The Lancet |volume=304 |issue=7872 |pages=61–63 |year=1974 |pmid=4137164 |doi=10.1016/S0140-6736(74)91631-6}}</ref> the name was officially recognised by the [[Organization:International Committee on Taxonomy of Viruses|International Committee on Taxonomy of Viruses]] four years later.<ref name="pmid43850">{{cite journal |author=Matthews RE |title=Third report of the International Committee on Taxonomy of Viruses. Classification and nomenclature of viruses |journal=Intervirology |volume=12 |issue=3–5 |pages=129–296 |year=1979 |pmid=43850 |doi=10.1159/000149081|doi-access=free }}</ref> In 1976, related viruses were described in several other species of animals.<ref name="pmid965097" /> These viruses, all causing acute gastroenteritis, were recognised as a collective pathogen affecting humans and other animals worldwide.<ref name="pmid77663">{{cite journal |vauthors=Flewett TH, Woode GN |title=The rotaviruses |journal=Archives of Virology |volume=57 |issue=1 |pages=1–23 |year=1978 |pmid=77663 |doi=10.1007/BF01315633 |pmc=7087197 }}</ref> Rotavirus serotypes were first described in 1980,<ref name="pmid2833405">{{cite journal |vauthors=Beards GM, Brown DW |s2cid=11547573 |title=The antigenic diversity of rotaviruses: significance to epidemiology and vaccine strategies |journal=European Journal of Epidemiology |volume=4 |issue=1 |pages=1–11 |year= 1988 |pmid=2833405 |doi=10.1007/BF00152685}}</ref> and in the following year, rotaviruses from humans were first grown in [[Biology:Cell culture|cell culture]]s derived from monkey kidneys, by adding [[Biology:Trypsin|trypsin]] (an enzyme found in the [[Biology:Duodenum|duodenum]] of mammals and now known to be essential for rotavirus to replicate) to the culture medium.<ref name="pmid6273696">{{cite journal |vauthors=Urasawa T, Urasawa S, Taniguchi K |title=Sequential passages of human rotavirus in MA-104 cells |journal=Microbiology and Immunology |volume=25 |issue=10 |pages=1025–1035 |year=1981 |pmid=6273696 |doi=10.1111/j.1348-0421.1981.tb00109.x |s2cid=25276891 |doi-access=free }}</ref> The ability to grow rotaviruses in culture accelerated the pace of research, and by the mid-1980s the first candidate vaccines were being evaluated.<ref name="pmid19072246">{{cite journal |vauthors=Ward RL, Bernstein DI |title=Rotarix: a rotavirus vaccine for the world |journal=Clinical Infectious Diseases |volume=48 |issue=2 |pages=222–228 |year =2009 |pmid=19072246 |doi=10.1086/595702 |doi-access=free }}</ref>

{{clear}}

== References ==
{{Reflist|35em}}

== External links ==

{{Medical resources
|  ICD10          = {{ICD10|A|08|0|a|00}}
|  ICD9           = {{ICD9|008.61}}
|  ICDO           =
|  OMIM           =
|  MedlinePlus    = 000252
|  eMedicineSubj  = emerg
|  eMedicineTopic = 401
|  eMedicine_mult =
|  DiseasesDB     = 11667
|  MeshID         = D012400
|ICD11={{ICD11|XN6N7}}}}

{{Viral systemic diseases}}
{{Baltimore classification}}
{{Consumer Food Safety}}
{{Taxonbar|from=Q164778}}

[[Category:Gastroenterology]]
[[Category:Pediatrics]]
[[Category:Virus genera]]

{{Sourceattribution|Rotavirus}}