View source for Biology:Alphavirus

{{Short description|Genus of viruses}}
{{Inline citations|date=May 2023}}}}
{{Virusbox
| image = Ijms-20-04657-g003.webp
| image_caption = Structure and genome of an alphavirus
| image2 = Alphavirus.png
| image2_alt = A computer-generated model of the surface of an "Alphavirus" derived by cryoelectron microscopy. The spike-like structures on the virion surface are trimers composed of heterodimers of the virion surface glycoproteins E1 and E2. These spikes are used by the virus to attach to susceptible animal cells
| image2_caption = A computer-generated model of the surface of an ''Alphavirus'' derived by cryoelectron microscopy. The spike-like structures on the virion surface are [[Biology:Protein trimer|trimers]] composed of heterodimers of the virion surface Glycoproteins E1 and E2. These spikes are used by the virus to attach to susceptible animal cells
| taxon = Alphavirus
| synonyms =
| synonyms_ref =
| subdivision_ranks = Species
| subdivision =
* ''Aura virus''
* ''[[Medicine:Barmah Forest virus|Barmah Forest virus]]''
* ''Bebaru virus''
* ''Caaingua virus''
* ''Cabassou virus''
* ''Chikungunya virus''
* ''Eastern equine encephalitis virus''
* ''Eilat virus''
* ''Everglades virus''
* ''Fort Morgan virus''
* ''Getah virus''
* ''[[Biology:Highlands J virus|Highlands J virus]]''
* ''Madariaga virus''
* ''Mayaro virus''
* ''[[Biology:Middelburg virus|Middelburg virus]]''
* ''Mosso das Pedras virus''
* ''Mucambo virus''
* ''Ndumu virus''
* ''O'nyong'nyong virus''
* ''Pixuna virus''
* ''Rio Negro virus''
* ''[[Medicine:Ross River virus|Ross River virus]]''
* ''Salmon pancreas disease virus''
* ''Semliki Forest virus''
* ''Sindbis virus''
* ''Southern elephant seal virus''
* ''Tonate virus''
* ''Trocara virus''
* ''Una virus''
* ''[[Medicine:Venezuelan equine encephalitis virus|Venezuelan equine encephalitis virus]]''
* ''[[Medicine:Western equine encephalitis virus|Western equine encephalitis virus]]''
* ''Whataroa virus''
}}<ref>{{Cite web |title=SAHIL |url=http://dx.doi.org/10.1163/1573-3912_islam_com_0972 |access-date=2023-07-06 |website=Encyclopaedia of Islam, Second Editiorajputn}}</ref>

'''''Alphavirus''''' is a genus of [[Biology:RNA virus|RNA virus]]es, the sole genus in the ''Togaviridae'' family. Alphaviruses belong to group IV of the [[Biology:Baltimore classification|Baltimore classification]] of [[Biology:Virus|virus]]es, with a positive-sense, single-stranded [[Biology:RNA|RNA]] genome. There are 32 alphaviruses, which infect various [[Biology:Vertebrate|vertebrate]]s such as humans, rodents, fish, birds, and larger mammals such as horses, as well as [[Biology:Invertebrate|invertebrate]]s. Alphaviruses that could infect both vertebrates and arthropods are referred dual-host alphaviruses, while insect-specific alphaviruses such as Eilat virus and Yada yada virus are restricted to their competent arthropod vector.<ref>{{Cite journal| vauthors = Elrefaey AM, Abdelnabi R, Rosales Rosas AL, Wang L, Basu S, Delang L |date=2020-08-31 |title=Understanding the Mechanisms Underlying Host Restriction of Insect-Specific Viruses |journal=Viruses |volume=12 |issue=9 |pages=964 |doi=10.3390/v12090964 |doi-access=free |pmid=32878245 |pmc=7552076}}</ref> Transmission between species and individuals occurs mainly via mosquitoes, making the alphaviruses a member of the collection of [[Medicine:Arbovirus|arbovirus]]es – or [[Biology:Arthropod|arthropod]]-borne viruses. Alphavirus particles are enveloped, have a 70&nbsp;nm diameter, tend to be spherical (although slightly [[Biology:Pleomorphism (microbiology)|pleomorphic]]), and have a 40&nbsp;nm isometric nucleocapsid.<ref name= ICTV >{{cite journal | vauthors = Chen R, Mukhopadhyay S, Merits A, Bolling B, Nasar F, Coffey LL, Powers A, Weaver SC | display-authors = 6 | title = ICTV Virus Taxonomy Profile: Togaviridae | journal = The Journal of General Virology | volume = 99 | issue = 6 | pages = 761–2 | date = June 2018 | pmid = 29745869 | doi = 10.1099/jgv.0.001072 | doi-access = free }}</ref>

==Genome==
{{Infobox protein family
| Symbol = Alpha_E1_glycop
| Name = Alpha_E1_glycop
| image = PDB 1rer EBI.jpg
| width =
| caption = Crystal structure of the [[Chemistry:Homotrimer|homotrimer]] of fusion glycoprotein E1 from Semliki Forest virus
| Pfam = PF01589
| Pfam_clan = 
| InterPro = IPR002548
| SMART =
| PROSITE =
| MEROPS =
| SCOP = 1rer
| TCDB = 1.G
| OPM family = 109
| OPM protein = 1rer
| CAZy =
| CDD =
}}
{{Infobox protein family
| Symbol = Alpha_E2_glycop
| Name = Alpha_E2_glycop
| image = PDB 1z8y EBI.jpg
| width =
| caption = Mapping the E2 glycoprotein of alphaviruses
| Pfam = PF00943
| Pfam_clan = 
| InterPro = IPR000936
| SMART =
| PROSITE =
| MEROPS =
| SCOP =
| TCDB = 1.G
| OPM family = 109
| OPM protein = 2yew
| CAZy =
| CDD =
}}
{{Infobox protein family
| Symbol = Alpha_E3_glycop
| Name = Alpha_E3_glycop
| image =
| width =
| caption =
| Pfam = PF01563
| Pfam_clan = 
| InterPro = IPR002533
| SMART =
| PROSITE =
| MEROPS =
| SCOP =
| TCDB = 1.G
| OPM family = 109
| OPM protein =
| CAZy =
| CDD =
}}
The alphaviruses are small, spherical, enveloped viruses with a genome of a single strand of positive-sense RNA. The total genome length ranges between 11,000 and 12,000 nucleotides, and has a [[Biology:Five-prime cap|5’ cap]] and a 3’ poly-A tail. The four non-structural protein genes are encoded in the 5′ two-thirds of the genome, while the three structural proteins are translated from a subgenomic mRNA colinear with the 3′ one-third of the genome.

There are two open reading frames (ORFs) in the genome, nonstructural and structural. The first is non-structural and encodes proteins (nsP1–nsP4) necessary for transcription and replication of viral RNA. The second encodes three [[Biology:Secondary structure|structural]] proteins: the core nucleocapsid [[Biology:Protein|protein]] C, and the envelope [[Biology:Protein|protein]]s P62 and E1, which associate as a heterodimer. The viral membrane-anchored surface glycoproteins are responsible for [[Biology:Receptor (biochemistry)|receptor]] recognition and entry into target [[Biology:Cell|cell]]s through membrane fusion.

===Structural proteins===
The proteolytic maturation of P62 into E2 and E3 causes a change in the viral surface. Together the E1, E2, and sometimes E3, [[Chemistry:Glycoprotein|glycoprotein]] "spikes" form an E1/E2 [[Biology:Protein dimer|dimer]] or an E1/E2/E3 trimer, where E2 extends from the centre to the vertices, E1 fills the space between the vertices, and E3, if present, is at the distal end of the spike.<ref name="pmid8107141">{{cite journal | author = Vénien-Bryan C, Fuller SD | title = The organization of the spike complex of Semliki Forest virus | journal = J. Mol. Biol. | volume = 236 | issue = 2 | pages = 572–83 |date=February 1994 | pmid = 8107141 | doi = 10.1006/jmbi.1994.1166 }}</ref> Upon exposure of the [[Biology:Virus|virus]] to the acidity of the [[Biology:Endosome|endosome]], E1 dissociates from E2 to form an E1 [[Chemistry:Homotrimer|homotrimer]], which is necessary for the fusion step to drive the [[Biology:Cell|cellular]] and viral [[Biology:Cell membrane|membrane]]s together. The alphaviral glycoprotein E1 is a class II viral fusion protein, which is structurally different from the class I fusion [[Biology:Proteins|proteins]] found in influenza virus and HIV. The [[Biology:Secondary structure|structure]] of the Semliki Forest virus revealed a structure that is similar to that of flaviviral glycoprotein E, with three structural domains in the same primary sequence arrangement.<ref name="pmid11301009">{{cite journal |vauthors=Lescar J, Roussel A, Wien MW, Navaza J, Fuller SD, Wengler G, Wengler G, Rey FA | title = The Fusion glycoprotein shell of Semliki Forest virus: an icosahedral assembly primed for fusogenic activation at endosomal pH | journal = Cell | volume = 105 | issue = 1 | pages = 137–48 |date=April 2001 | pmid = 11301009 | doi = 10.1016/S0092-8674(01)00303-8 | s2cid = 16535677 | doi-access = free }}</ref> The E2 glycoprotein functions to interact with the nucleocapsid through its [[Biology:Cytoplasm|cytoplasm]]ic domain, while its ectodomain is responsible for binding a cellular [[Biology:Receptor (biochemistry)|receptor]]. Most alphaviruses lose the peripheral protein E3, but in Semliki viruses it remains associated with the viral surface.

===Nonstructural proteins===
Four nonstructural proteins (nsP1–4) which are produced as a single polyprotein constitute the virus' replication machinery.<ref name=Shin2012>{{cite journal |vauthors=Shin G, Yost SA, Miller MT, Elrod EJ, Grakoui A, Marcotrigiano J |title=Structural and functional insights into alphavirus polyprotein processing and pathogenesis |journal=Proc Natl Acad Sci U S A |volume=109 |issue=41 |pages=16534–9 |date=2012 |doi=10.1073/pnas.1210418109   |pmid=23010928 |pmc=3478664|bibcode=2012PNAS..10916534S |doi-access=free }}</ref> The processing of the polyprotein occurs in a highly regulated manner, with cleavage at the P2/3 junction influencing RNA template use during genome replication. This site is located at the base of a narrow cleft and is not readily accessible. Before cleavage, nsP3 creates a ring structure that encircles nsP2. These two proteins have an extensive interface.

Mutations in nsP2 that produce noncytopathic viruses or a temperature sensitive phenotypes cluster at the P2/P3 interface region. P3 mutations opposite the location of the nsP2 noncytopathic mutations prevent efficient cleavage of P2/3. This in turn affects RNA infectivity altering viral RNA production levels.

==Virology==

The virus has a 60–70 nanometer diameter. It is enveloped, spherical and has a positive-strand RNA genome of ~12 kilobases. The genome encodes two polyproteins. The first polyprotein consists of four non-structural units: in order from the N terminal to the C terminal - nsP1, nsP2, nsP3, and nsP4. The second is a structural polyprotein composed of five expression units: from the N terminal to the C terminal - Capsid, E3, E2, 6K and E1. A sub genomic positive strand RNA - the 26S RNA - is replicated from a negative-stranded RNA intermediate. This serves as template for the synthesis of viral structural proteins. Most alphaviruses have conserved domains involved in regulation of viral RNA synthesis.

The nucleocapsid, 40 nanometers in diameter, contains 240 copies of the capsid protein and has a T = 4 icosahedral symmetry. The E1 and E2 viral glycoproteins are embedded in the lipid bilayer. Single E1 and E2 molecules associate to form heterodimers. The E1–E2 heterodimers form one-to-one contacts between the E2 protein and the nucleocapsid monomers. The E1 and E2 proteins mediate contact between the virus and the host cell.

Several receptors have been identified. These include [[Biology:Prohibitin|prohibitin]], [[Chemistry:Phosphatidylserine|phosphatidylserine]], [[Chemistry:Glycosaminoglycan|glycosaminoglycan]]s and [[Biology:ATP synthase|ATP synthase]] β subunit (ref needed).

Replication occurs within the cytoplasm, specifically in areas termed "spherules" separated by plasma membrane invaginations from the rest. Each complex occupies one such area of about 50-nm in inner diameter.<ref>{{cite journal |last1=Spuul |first1=P |last2=Balistreri |first2=G |last3=Hellström |first3=K |last4=Golubtsov |first4=AV |last5=Jokitalo |first5=E |last6=Ahola |first6=T |title=Assembly of alphavirus replication complexes from RNA and protein components in a novel trans-replication system in mammalian cells. |journal=Journal of Virology |date=May 2011 |volume=85 |issue=10 |pages=4739–51 |doi=10.1128/JVI.00085-11 |pmid=21389137 |pmc=3126202}}</ref>

Virions mature by budding through the plasma membrane, where virus-encoded surface glycoproteins E2 and E1 are assimilated. These two glycoproteins are the targets of numerous serologic reactions and tests including neutralization and hemagglutination inhibition. The alphaviruses show various degrees of antigenic cross-reactivity in these reactions and this forms the basis for the seven antigenic complexes, 32 species and many subtypes and varieties. The E2 protein is the site of most neutralizing epitopes, while the E1 protein contains more conserved, cross-reactive epitopes.

==Evolution==
A study of this taxon suggests that this group of viruses had a marine origin—specifically the Southern Ocean—and that they have subsequently spread to both the Old and New World.<ref name="pmid22190718">{{cite journal |vauthors=Forrester NL, Palacios G, Tesh RB, Savji N, Guzman H, Sherman M, Weaver SC, Lipkin WI | title = Genome scale phylogeny of the Alphavirus genus suggests a marine origin | journal = J Virol | volume = 86| issue = 5| pages = 2729–38|date=December 2011 | pmid = 22190718 | doi = 10.1128/JVI.05591-11 | pmc = 3302268}}</ref>

There are three subgroups in this genus: the Semliki Forest virus subgroup (Semliki Forest, O'nyong-nyong and Ross River viruses); the eastern equine encephalitis virus subgroup (eastern equine encephalitis and Venezuelan equine encephalitis viruses) and the Sindbis virus subgroup.<ref name=Levinson1990>{{cite journal |vauthors=Levinson RS, Strauss JH, Strauss EG | year = 1990 | title = Complete sequence of the genomic RNA of O'nyong-nyong virus and its use in the construction of alphavirus phylogenetic trees | journal = Virology | volume = 175 | issue = 1| pages = 110–123 | doi=10.1016/0042-6822(90)90191-s| pmid = 2155505 }}</ref> Sindbis virus, geographically restricted to the Old World, is more closely related to the eastern equine encephalitis subgroup, which are New World viruses, than it is to the Semliki Forest virus subgroup which is also found in the Old World.

==Taxonomy==
The following species are assigned to the genus:<ref>{{cite web |title=Virus Taxonomy: 2020 Release |url=https://ictv.global/taxonomy |publisher=International Committee on Taxonomy of Viruses (ICTV) |date=March 2021 |access-date=15 May 2021}}</ref>
{{div col|colwidth=20em}}
* ''Aura virus''
* ''[[Medicine:Barmah Forest virus|Barmah Forest virus]]''
* ''Bebaru virus''
* ''Caaingua virus''
* ''Cabassou virus''
* ''Chikungunya virus''
* ''Eastern equine encephalitis virus''
* ''Eilat virus''
* ''Everglades virus''
* ''Fort Morgan virus''
* ''Getah virus''
* ''[[Biology:Highlands J virus|Highlands J virus]]''
* ''Madariaga virus''
* ''Mayaro virus''
* ''[[Biology:Middelburg virus|Middelburg virus]]''
* ''Mosso das Pedras virus''
* ''Mucambo virus''
* ''Ndumu virus''
* ''O'nyong'nyong virus''
* ''Pixuna virus''
* ''Rio Negro virus''
* ''[[Medicine:Ross River virus|Ross River virus]]''
* ''Salmon pancreas disease virus''
* ''Semliki Forest virus''
* ''Sindbis virus''
* ''Southern elephant seal virus''
* ''Tonate virus''
* ''Trocara virus''
* ''Una virus''
* ''[[Medicine:Venezuelan equine encephalitis virus|Venezuelan equine encephalitis virus]]''
* ''[[Medicine:Western equine encephalitis virus|Western equine encephalitis virus]]''
* ''Whataroa virus''
{{div col end}}

The seven complexes are:

:'''Barmah Forest virus complex'''
::[[Medicine:Barmah Forest virus|Barmah Forest virus]]

:'''Eastern equine encephalitis complex'''
::Eastern equine encephalitis virus (seven antigenic types)

:'''Middelburg virus complex'''
::[[Biology:Middelburg virus|Middelburg virus]]

:'''Ndumu virus complex'''
::Ndumu virus

:'''Semliki Forest virus complex'''
::Bebaru virus<!--species of its own, not just subtype of Ross River virus, due to ICTV MSL (#33) Fall 2018-->
::Chikungunya virus
::Getah virus
::Mayaro virus<!--same as Bebaru virus-->
:::Subtype: Una virus
::O'nyong'nyong virus
:::Subtype: Igbo-Ora virus
::[[Medicine:Ross River virus|Ross River virus]]
:::Subtype: Sagiyama virus
::Semliki Forest virus
:::Subtype: Me Tri virus

:'''Venezuelan equine encephalitis complex'''
::Cabassou virus
::Everglades virus
::Mosso das Pedras virus
::Mucambo virus
::Paramana virus
::Pixuna virus
::Rio Negro virus
::Trocara virus
:::Subtype: Bijou Bridge virus
::[[Medicine:Venezuelan equine encephalitis virus|Venezuelan equine encephalitis virus]]

:'''Western equine encephalitis complex'''
::Aura virus
::Babanki virus
::Kyzylagach virus
::Sindbis virus
::[[Medicine:Pogosta disease|Ockelbo virus]]
::Whataroa virus

:::'''Recombinants within this complex'''
:::Buggy Creek virus
:::Fort Morgan virus
:::[[Biology:Highlands J virus|Highlands J virus]]
:::[[Medicine:Western equine encephalitis virus|Western equine encephalitis virus]]

:'''Unclassified'''
::Eilat virus
::Mwinilunga alphavirus
::Salmonid Alphavirus
::Southern elephant seal virus
<!--::[[Biology:Taï Forest virus|Taï Forest virus]] 'close relative of ''Ebola virus''. But ''Ebola virus''is ''Filoviridae'', not ''Togaviridae'':''Alphavirus''. Official names don't have diacritic symbols due to ICTV-->
::Tonate virus
::Caaingua virus<ref>{{cite journal | vauthors = Tschá MK, Suzukawa AA, Gräf T, Piancini LD, da Silva AM, Faoro H, Riediger IN, Medeiros LC, Wowk PF, Zanluca C, Duarte Dos Santos CN | display-authors = 6 | title = Identification of a novel alphavirus related to the encephalitis complexes circulating in southern Brazil | journal = Emerging Microbes & Infections | volume = 8 | issue = 1 | pages = 920–933 | date = 2019 | pmid = 31237479 | doi = 10.1080/22221751.2019.1632152 | pmc = 6598490 | doi-access = free }}</ref>

===Notes===
Barmah Forest virus is related to the Semliki Forest virus. Middelburg virus, although classified as a separate complex, may be a member of the Semliki Forest virus group.

It seems likely that the genus evolved in the Old World from an insect-borne plant virus.<ref name="pmid11581380">{{cite journal |vauthors=Powers AM, Brault AC, Shirako Y, Strauss EG, Kang W, Strauss JH, Weaver SC | title = Evolutionary relationships and systematics of the alphaviruses | journal = J. Virol. | volume = 75 | issue = 21 | pages = 10118–31 |date=November 2001 | pmid = 11581380 | pmc = 114586 | doi = 10.1128/JVI.75.21.10118-10131.2001 }}</ref>

Sindbis virus may have originated in South America.<ref name="pmid20420530">{{cite journal |vauthors=Lundström JO, Pfeffer M | title = Phylogeographic structure and evolutionary history of Sindbis virus | journal = Vector Borne Zoonotic Dis. | volume = 10 | issue = 9 | pages = 889–907 |date=November 2010 | pmid = 20420530 | doi = 10.1089/vbz.2009.0069 }}</ref> The equine encephalitis viruses and the Sindbis virus are related.

The Old World and New World viruses appears to have diverged between 2000 and 3000 years ago.<ref name="pmid8105605">{{cite journal |vauthors=Weaver SC, Hagenbaugh A, Bellew LA, Netesov SV, Volchkov VE, Chang GJ, Clarke DK, Gousset L, Scott TW, Trent DW | title = A comparison of the nucleotide sequences of eastern and western equine encephalomyelitis viruses with those of other alphaviruses and related RNA viruses | journal = Virology | volume = 197 | issue = 1 | pages = 375–90 |date=November 1993 | pmid = 8105605 | doi =  10.1006/viro.1993.1599}}</ref> Divergence between the Venezuelan equine encephalitis virus and the eastern equine virus appears to have been ~1400 years ago.<ref name="pmid1318187">{{cite journal |vauthors=Weaver SC, Rico-Hesse R, Scott TW | title = Genetic diversity and slow rates of evolution in New World alphaviruses | journal = Curr. Top. Microbiol. Immunol. | series = Current Topics in Microbiology and Immunology | volume = 176 | pages = 99–117 | year = 1992 | doi = 10.1007/978-3-642-77011-1_7 | pmid = 1318187 | isbn = 978-3-642-77013-5 }}</ref>

The fish infecting clade appears to be basal to the other species.

The southern elephant seal virus appears to be related to the Sinbis clade.

==Pathogenesis and immune response==
{{Unsourced section|date=May 2023}}
{| class="wikitable" style="float: right; font-size: 85%; margin-left: 1em; max-width: 50%;"
|+ Medically important alphaviruses
|-
! scope="col" | Virus
! scope="col" | Human Disease
! scope="col" | Vertebrate Reservoir
! scope="col" | Distribution
|-
| [[Medicine:Barmah Forest virus|Barmah Forest virus]]
| {{ubl
  | Fever, malaise, rash,
  | joint pain, muscle tenderness
  }}
| Humans
| Australia
|-
| Chikungunya virus
| Rash, arthritis
| Primates, humans
| Africa, Latin America, {{wipe|India}}, SE Asia
|-
| Eastern equine encephalitis virus
| Encephalitis
| Birds
| [[Earth:Americas|Americas]]
|-
| Mayaro virus
| Rash, arthritis
| Primates, humans
| [[Earth:South America|South America]]
|-
| O'nyong'nyong virus
| Rash, arthritis
| [[Biology:Primate|Primate]]s, Humans
| Africa
|-
| [[Medicine:Ross River virus|Ross River virus]]
| Rash, arthritis
| Mammals, humans
| Australia, [[Earth:Oceania|South Pacific]]
|-
| Semliki Forest virus
| Rash, arthritis
| Birds
| Africa
|-
| Sindbis virus
| Rash, arthritis
| Birds
| [[Earth:Europe|Europe]], [[Earth:Africa|Africa]], {{wipe|Australia}}
|-
| Tonate virus
| Encephalitis
| Humans
| South America
|-
| Una virus
| Rash, arthritis
| Primates, humans
| [[Earth:South America|South America]]
|-
| [[Medicine:Venezuelan equine encephalitis virus|Venezuelan equine encephalitis virus]]
| Encephalitis
| [[Biology:Rodent|Rodent]]s, horses
| Americas
|-
| [[Medicine:Western equine encephalitis virus|Western equine encephalitis virus]]
| Encephalitis
| Birds, mammals
| [[Earth:North America|North America]]
|}

There are many alphaviruses distributed around the world with the ability to cause human disease. Infectious [[Medicine:Arthritis|arthritis]], [[Medicine:Encephalitis|encephalitis]], rashes and [[Medicine:Fever|fever]] are the most commonly observed symptoms. Larger mammals such as humans and horses are usually dead-end hosts or play a minor role in viral transmission; however, in the case of Venezuelan equine encephalitis the virus is mainly amplified in horses. In most other cases the virus is maintained in nature in mosquitoes, rodents and birds.

Terrestrial alphavirus infections are spread by insect vectors such as mosquitoes. Once a human is bitten by the infected mosquito, the virus can gain entry into the bloodstream, causing [[Medicine:Viremia|viremia]]. The alphavirus can also get into the [[Biology:Central nervous system|CNS]] where it is able to grow and multiply within the neurones. This can lead to [[Medicine:Encephalitis|encephalitis]], which can be fatal.

When an individual is infected with this particular virus, its immune system can play a role in clearing away the virus particles. Alphaviruses are able to cause the production of interferons. Antibodies and T cells are also involved. The neutralizing antibodies also play an important role to prevent further infection and spread.

==Diagnosis, prevention, and control==
Diagnoses is based on clinical samples from which the virus can be easily isolated and identified.  There are no alphavirus vaccines currently available.  Vector control with repellents, protective clothing, breeding site destruction, and spraying are the preventive measures of choice.{{citation needed|date=May 2023}}

==Research==
{{Unsourced section|date=May 2023}}
Alphaviruses are of interest to [[Biology:Gene therapy|gene therapy]] researchers, in particular the Ross River virus, Sindbis virus, Semliki Forest virus, and Venezuelan equine encephalitis virus have all been used to develop viral vectors for gene delivery. Of particular interest are the chimeric viruses that may be formed with alphaviral envelopes and retroviral capsids. Such chimeras are termed pseudotyped viruses.  Alphaviral envelope pseudotypes of retroviruses or lentiviruses are able to integrate the genes that they carry into the expansive range of potential host cells that are recognized and infected by the alphaviral envelope proteins E2 and E1. The stable integration of viral genes is mediated by the retroviral interiors of these vectors. There are limitations to the use of alphaviruses in the field of [[Biology:Gene therapy|gene therapy]] due to their lack of targeting, however, through the introduction of variable antibody domains in a non-conserved loop in the structure of E2, specific populations of cells have been targeted. Furthermore, the use of whole alphaviruses for gene therapy is of limited efficacy both because several internal alphaviral proteins are involved in the induction of apoptosis upon infection and also because the alphaviral capsid mediates only the transient introduction of mRNA into host cells. Neither of these limitations extend to alphaviral envelope pseudotypes of retroviruses or lentiviruses. However, the expression of Sindbis virus envelopes may lead to apoptosis, and their introduction into host cells upon infection by Sindbis virus envelope pseudotyped retroviruses may also lead to cell death.  The toxicity of Sindbis viral envelopes may be the cause of the very low production titers realized from packaging cells constructed to produce Sindbis pseudotypes. Another branch of research involving alphaviruses is in vaccination. Alphaviruses are apt to be engineered to create [[Biology:Replicon (genetics)|replicon]] vectors which efficiently induce humoral and T-cell immune responses. They could therefore be used to vaccinate against viral, bacterial, protozoan, and tumor antigens.

==History==
Initially, the ''Togaviridae'' family included what are now called the'' [[Biology:Flaviviridae|Flaviviruses]]'', within the ''Alphavirus'' genus. The flaviviruses were formed into their own family when sufficient differences with the alphaviruses were noted due to the development of sequencing.<ref name=Stanford>{{cite web|title=Togaviridae|url=https://web.stanford.edu/group/virus/toga/|publisher=stanford.edu}}</ref> Rubella virus was formerly included in the family ''Togaviridae'' in its own genus ''Rubivirus'', but is now classified in its own family ''Matonaviridae''.<ref>{{cite web |title=ICTV Taxonomy List |url=https://ictv.global/taxonomy|access-date=5 May 2020}}</ref> '''''Alphavirus''''' is now the sole genus in the family.
* 1930 – [[Medicine:Western equine encephalitis virus|Western equine encephalitis virus]] is first isolated in the United States (the first alphavirus ever isolated)
* 1933 – Eastern equine encephalitis virus is first isolated in the United States.
* 1938 – [[Medicine:Venezuelan equine encephalitis virus|Venezuelan equine encephalitis]] is isolated.
* 1941 – Western equine encephalitis [[Medicine:Epidemic|epidemic]] is seen in the United States. It affects 300,000 horses and 3,336 humans.
* 1941 – Norman Gregg notices large number of children with cataracts following a rubella outbreak. This and other defects are then categorized under the [[Medicine:Congenital rubella syndrome|congenital rubella syndrome]].
* 1942 – Semliki Forest virus is isolated in Buliyama, Bwamba County, Uganda.
* 1952 – Sindbis virus is isolated in the Sindbis health district, {{cvt|40|mi}} north of [[Place:Cairo|Cairo, Egypt]].
* 1959 – [[Medicine:Ross River virus|Ross River virus]] is isolated from ''[[Biology:Aedes vigilax|Aedes vigilax]]'' mosquitoes (now known as ''[[Biology:Ochlerotatus|Ochlerotatus]] vigilax'')<ref>{{cite web |url=http://medent.usyd.edu.au/arbovirus/mosquit/aedesvigilax.htm |title=Aedes vigilax |access-date=2010-06-05 |work=NSW Arbovirus Surveillance & Vector Monitoring Program |publisher=The New South Wales Arbovirus Surveillance and Mosquito Monitoring Program |quote=Note that 'Ochlerotatus vigilax' prior to 2000, was known as 'Aedes vigilax' |archive-date=19 March 2018 |archive-url=https://web.archive.org/web/20180319143114/http://medent.usyd.edu.au/arbovirus/mosquit/aedesvigilax.htm |url-status=dead }}</ref> which were trapped at the Ross River in Australia.
* 1963 – Ross River virus, which causes epidemic polyarthritis (mostly seen in Australia), is isolated by Doherty and colleagues.<ref>{{cite journal | vauthors = Doherty RL, Carley JG, Best JC | title = Isolation of Ross River virus from man | journal = The Medical Journal of Australia | volume = 1 | issue = 21 | pages = 1083–4 | date = May 1972 | doi = 10.5694/j.1326-5377.1972.tb116646.x | pmid = 5040017 | s2cid = 13048176 }}</ref>
* 1971 – Last epidemic of Venezuelan equine encephalitis is seen in horses in southern {{wipe|Texas}}.<ref>{{cite journal| vauthors = Calisher CH | title = Medically important arboviruses of the United States and Canada | journal = Clinical Microbiology Reviews | volume = 7 | issue = 1 | pages = 89–116 | date = January 1994 | pmid = 8118792 | pmc = 358307 | doi = 10.1128/CMR.7.1.89 }}</ref>
* 1986 – Barmah Forest virus is identified as causing human disease in Australia.<ref>{{cite journal | vauthors = Boughton CR, Hawkes RA, Naim HM | title = Illness caused by a Barmah Forest-like virus in New South Wales | journal = The Medical Journal of Australia | volume = 148 | issue = 3 | pages = 146–7 | date = February 1988 | doi = 10.5694/j.1326-5377.1988.tb112780.x | pmid = 2828896 | s2cid = 30837260 }}</ref>
* 2001 – Scientists solved the [[Chemistry:Crystal structure|crystal structure]] of the glycoprotein shell of the Semliki Forest virus.
* 2005–2006 – Large epidemic of the chikungunya virus on the island of La Réunion and the surrounding islands in the [[Earth:Indian Ocean|Indian Ocean]]<ref>{{cite journal | vauthors = Tsetsarkin K, Higgs S, McGee CE, De Lamballerie X, Charrel RN, Vanlandingham DL | title = Infectious clones of Chikungunya virus (La Réunion isolate) for vector competence studies | journal = Vector Borne and Zoonotic Diseases | volume = 6 | issue = 4 | pages = 325–37 | year = 2006 | pmid = 17187566 | doi = 10.1089/vbz.2006.6.325 }}</ref>
* 2006 – Major epidemic of the chikungunya virus in India with over 1.5 million cases reported<ref>{{cite journal | vauthors = Lahariya C, Pradhan SK | title = Emergence of chikungunya virus in Indian subcontinent after 32 years: A review | journal = Journal of Vector Borne Diseases | volume = 43 | issue = 4 | pages = 151–60 | date = December 2006 | pmid = 17175699 }}</ref>

==See also==
* Alphavirus infection

==Sources==
{{refbegin}}
* {{cite web|url=http://virology-online.com/viruses/Arboviruses2.htm|title=Arboviruses|website=Virology-online}}
* {{cite web|url=http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/73010000.htm|archive-url=https://web.archive.org/web/20060212195722/http://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/73010000.htm|url-status=dead|archive-date=2006-02-12|title=ICTV Sources|website=ICTV}}
* {{cite journal |title=Alphavirus vectors: from protein production to gene therapy |first1=C. |last1=Smerdou |first2=P. |last2=Liljestrom |journal=Gene Therapy and Regulation |volume=1 |issue=1 |date=2000 |pages=33–63 |issn=1568-5586 |doi=10.1163/156855800744520 |doi-access=free }}
* {{cite journal | vauthors = Rayner JO, Dryga SA, Kamrud KI | title = Alphavirus vectors and vaccination | journal = Reviews in Medical Virology | volume = 12 | issue = 5 | pages = 279–96 | year = 2002 | pmid = 12211042 | doi = 10.1002/rmv.360 | s2cid = 21432844 }}
* {{cite journal |first1=Céline |last1=Rhême |first2=Markus U. |last2=Ehrengruber |first3=Denis |last3=Grandgirard |title=Alphaviral cytotoxicity and its implication in vector development |journal=Experimental Physiology |year=2005 |volume=90 |issue=1 |pages=45–52 |doi=10.1113/expphysiol.2004.028142 |pmid=15542620|doi-access= }}
* {{cite book |first1=Alan L. |last1=Schmaljohn |first2=David |last2=McClain |chapter=54. Alphaviruses (Togaviridae) and Flaviviruses (Flaviviridae) |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK7633/ |editor-first=Samuel |editor-last=Baron |title=Medical Microbiology |publisher=University of Texas Medical Branch at Galveston |edition=4th |date=1996 |isbn=0-9631172-1-1 |pages= |url=https://www.ncbi.nlm.nih.gov/books/NBK7627/ |id=NBK7633 |pmid=21413253}}
{{refend}}

==References==
{{Reflist|2}}

==External links==
* [https://ictv.global/report/togaviridae '''ICTV Report ''Togaviridae''''']
* [http://www.expasy.org/viralzone/all_by_species/625.html '''Viralzone''': Alphavirus]
* [https://www.viprbrc.org/brc/home.spg?decorator=toga Virus Pathogen Database and Analysis Resource (ViPR): Togaviridae]

{{InterPro content|IPR000936}}

{{InterPro content|IPR002533}}

{{InterPro content|IPR002548}}

{{Baltimore classification}}

{{Taxonbar|from=Q1111605}}

[[Category:Togaviruses]]
[[Category:Virus genera]]

{{Sourceattribution|Alphavirus}}