View source for Biology:Drosophila X virus

{{Short description|Species of virus}}
{{virusbox
| parent = Entomobirnavirus
| species = Drosophila X virus
}}
'''Drosophila X virus''' (DXV) belongs to the ''[[Biology:Birnaviridae|Birnaviridae]]'' family of viruses. ''Birnaviridae'' currently consists of three genera. The first genus is ''Entomobirnavirus'', which contains DXV.<ref name=chung>{{Cite journal
 | pmid = 8918922
| year = 1996
| last1 = Chung
| first1 = H. K.
| title = Sequence analysis of the bicistronic Drosophila X virus genome segment a and its encoded polypeptides
| journal = Virology
| volume = 225
| issue = 2
| pages = 359–68
| last2 = Kordyban
| first2 = S
| last3 = Cameron
| first3 = L
| last4 = Dobos
| first4 = P
| doi = 10.1006/viro.1996.0610
| doi-access = free
}}</ref> The next genus is ''Aquabirnavirus'', containing [[Biology:Infectious pancreatic necrosis virus|infectious pancreatic necrosis virus]] (IPNV).<ref name=chung/> The last genus is ''Avibirnavirus'', which contains [[Biology:Infectious bursal disease virus|infectious bursal disease virus]] (IBDV).<ref name=chung/> All of these genera contain homology in three specific areas of their transcripts. The homology comes from the amino and carboxyl regions of preVP2, a small 21-residue-long domain near the carboxyl terminal of VP3, and similar small ORFs sequences.<ref name=chung/>

DXV was named after ''[[Biology:Drosophila melanogaster|Drosophila melanogaster]]'', where it was first isolated. DXV was first isolated and named in 1978.<ref name=Teninges/> DXV was discovered as a contaminant in adult ''D. melanogaster'' while studying rhabdoviruses.<ref name=Teninges/> Assay results of DXV showed that DXV induces sensitivity to both carbon dioxide and [[Chemistry:Amidogen|NH<sub>2</sub>]], which suggests general anoxia. Therefore, the pathogenic pathway for DXV leads to anoxia sensitivity and death of ''D. melanogaster''.<ref name=Teninges/> By negative contrast electron microscopy the DXV components were first visualized.<ref name=Teninges/> The origin of DXV is unknown and unclear. It was thought that DXV could have been pre-existent in ''Drosophila'' broods in a non-pathogenic form. Additionally, it was speculated that DXV might have originated as a contaminant from fetal calf serum in infection type studies because it was documented that endogenous bovine viruses were already in fetal calf serum.<ref>{{Cite journal
 | pmid = 898680
| year = 1977
| last1 = Igarashi
| first1 = A
| title = Evolution and properties of Aedes albopictus cell cultures persistently infected with sindbis virus
| journal = Virology
| volume = 82
| issue = 1
| pages = 69–83
| last2 = Koo
| first2 = R
| last3 = Stollar
| first3 = V
 | doi=10.1016/0042-6822(77)90033-2
}}</ref>

==Structure, genome, and replication==
[[File:DXV genome.jpg|thumb|Drosophila X virus genome has two segments: segment A & segment B.]]
DXV is a Baltimore Class III naked (non-enveloped) virus. The capsid of this protein contains an icosahedral geometry (T=13) consisting of 260 trimeric VP2 capsomeres. Specifically, DXV contains a bi-segmented dsRNA genome.<ref name=chung/> Both segments of the DXV genome contain 5’ terminal GGA triplet and a 3’ terminal CCC triplet consensus, which is consistent with birnaviridae (Shwed, 2002). The segment A genome is 3360-bp in length.<ref name=chung/> Segment A encodes a polyprotein sequence as follows: NH2-preVP2-VP4-VP3-COOH. This segment contains a large and small ORF. The segment B genome is 2991-bp in length.<ref name=chung/> Segment B encodes a polypeptide sequence as follows: NH2-VP1-COOH.<ref name=shwed>{{Cite journal
 | pmid = 12069523
| year = 2002
| last1 = Shwed
| first1 = P. S.
| title = Birnavirus VP1 proteins form a distinct subgroup of RNA-dependent RNA polymerases lacking a GDD motif
| journal = Virology
| volume = 296
| issue = 2
| pages = 241–50
| last2 = Dobos
| first2 = P
| last3 = Cameron
| first3 = L. A.
| last4 = Vakharia
| first4 = V. N.
| last5 = Duncan
| first5 = R
| doi = 10.1006/viro.2001.1334
| doi-access = free
}}</ref> The 5’ UTR of segment B is homologous to segment A, but unlike segment A, there is only one ORF.<ref name=shwed/> Unusually, VP1 can be in two forms; as a free RdRp and as the genome-liked protein (VpG) that attaches to both 5’ end segments of the DXV through a Ser-5’-GMP phosphodiester bond.<ref name=pmid191 >{{Cite journal
 | pmid = 1919532
| year = 1991
| last1 = Calvert
| first1 = J. G.
| title = Characterization of the VPg-dsRNA linkage of infectious pancreatic necrosis virus
| journal = The Journal of General Virology
| volume = 72
| pages = 2563–7
| last2 = Nagy
| first2 = E
| last3 = Soler
| first3 = M
| last4 = Dobos
| first4 = P
 | doi=10.1099/0022-1317-72-10-2563
 | issue=10
| doi-access = free
}}</ref> The replication of DXV follows the characterized dsRNA virus replication cycle.<ref>{{Cite journal
 | pmid = 6774107
| pmc = 288596
| year = 1980
| last1 = Bernard
| first1 = J
| title = Drosophila X virus RNA polymerase: Tentative model for in vitro replication of the double-stranded virion RNA
| journal = Journal of Virology
| volume = 33
| issue = 2
| pages = 717–23
| doi = 10.1128/JVI.33.2.717-723.1980
}}</ref>

The large ORF of segment A consists of 3069 nucleotides.<ref name=chung/> The UTRs are characterized as 107-bp on 5’ side and 157-bp on 3’ end.<ref name=chung/> The start codons can be at either position 102, or two codons downstream at position 108. However, the initiation codon starts at the 108-bp.<ref name=chung/> The translation of the large ORF transcript produces a 114-kDa polyprotein.<ref name=chung/> The mature VP4 protein, viral protease, assists this process to increase the processing of the polyprotein to generate preVP2 capsid protein, VP3 viral ribonucleoprotein (RNP), and additional VP4 proteins.<ref name=chung/> In addition VP3 proteins can associate with pre-VP2 as a structural protein<ref>{{Cite journal
 | pmid = 19933276
| pmc = 2823505
| year = 2010
| last1 = Saugar
| first1 = I
| title = Electrostatic interactions between capsid and scaffolding proteins mediate the structural polymorphism of a double-stranded RNA virus
| journal = Journal of Biological Chemistry
| volume = 285
| issue = 6
| pages = 3643–50
| last2 = Irigoyen
| first2 = N
| last3 = Luque
| first3 = D
| last4 = Carrascosa
| first4 = J. L.
| last5 = Rodríguez
| first5 = J. F.
| last6 = Castón
| first6 = J. R.
| doi = 10.1074/jbc.M109.075994
| doi-access = free
}}</ref> and with VP1 to function as a transcriptional activator.<ref>{{Cite journal
 | pmid = 18077388
| pmc = 2154467
| year = 2007
| last1 = Garriga
| first1 = D
| title = Activation mechanism of a noncanonical RNA-dependent RNA polymerase
| journal = Proceedings of the National Academy of Sciences
| volume = 104
| issue = 51
| pages = 20540–5
| last2 = Navarro
| first2 = A
| last3 = Querol-Audí
| first3 = J
| last4 = Abaitua
| first4 = F
| last5 = Rodríguez
| first5 = J. F.
| last6 = Verdaguer
| first6 = N
| doi = 10.1073/pnas.0704447104
| bibcode = 2007PNAS..10420540G
| doi-access = free
}}</ref>

The small ORF of segment A consists of 711 nucleotides.<ref name=chung/> This ORF is in a location that extends across VP4/VP3 junction, although the precise position is unknown.<ref name=chung/> The mechanism for transcribing the small ORF is unknown. However, the possibility of ribosomal frameshifting has been ruled out since the small ORF site does not contain the characteristic hallmarks, such the 7 nucleotide long “slippery sequence” or downstream pseudoknot that is seen in other members of ''Birnaviridae''. It is hypothesized the small ORF is translated in a mechanism that uses subgenomic transcripts.<ref name=chung/> In any case, the translation of the small ORF transcript produces a 27-kDa polypeptide.<ref name=chung/> This polypeptide consists of 28 of basic, mainly arginine, residues. However this polypeptide has not been detected in infected cells.{{cn|date=October 2022}}

The segment B transcript encodes it encodes a 112.8-kDa VP1 polypeptide once translated.<ref name=shwed/> This polypeptide has been characterized to be the RNA-dependent RNA polymerase (RdRp) and the VpG.<ref name=pmid191 /> This polypeptide is 977 amino acids in length, making it the largest encoded RdRp in the ''Birnaviridae'' family.<ref name=shwed/> The RdRp contains a consensus GTP-binding site and is thought to contain self-guanylylation activity, making it consistent with the ''Birnaviridae'' RdRp capacity.<ref name=shwed/>

==Tropism==
Currently, DXV does not infect vertebrates. It is known that invertebrates, such as insects, are hosts for DXV, but their specific tissue tropism is not known for certain.<ref name=Tsai>{{Cite journal | doi = 10.1128/AEM.02248-07| title = Drosophila melanogaster Mounts a Unique Immune Response to the Rhabdovirus Sigma virus| journal = Applied and Environmental Microbiology| volume = 74| issue = 10| pages = 3251–3256| year = 2008| last1 = Tsai | first1 = C. W.| last2 = McGraw | first2 = E. A.| last3 = Ammar | first3 = E. -D. | last4 = Dietzgen | first4 = R. G.| last5 = Hogenhout | first5 = S. A. | pmid=18378641 | pmc=2394955}}</ref> Tracheal cells were thought to be a possible target because there is evidence that ''Drosophila'' flies that are infected by DXV suffered from lack of oxygen supply to their tissues, which eventually leads to death.<ref name=Teninges>{{Cite journal | doi = 10.1099/0022-1317-42-2-241| title = Isolation and Biological Properties of Drosophila X Virus| journal = Journal of General Virology| volume = 42| issue = 2| pages = 241–254| year = 1979| last1 = Teninges | first1 = D.| last2 = Ohanessian | first2 = A.| last3 = Richard-Molard | first3 = C.| last4 = Contamine | first4 = D.| doi-access = free}}</ref> Based on previous studies, DXV was unsuccessfully cultured in vertebrate cells lines and mouse brain.{{cn|date=October 2022}}

==Genetic variability==
It has not been shown yet that DXV naturally infects ''Drosophila'' flies therefore; there are no wild-type strains of DXV. The Culex Y virus (CYV) is a tentative member of the genus that DXV is in. It has been proposed that CYV could act as a wild-type counterpart in studies that rely on DXV.<ref name=Zhou>{{Cite journal
 | pmid = 23550641
| pmc = 3695692
| year = 2013
| last1 = Zhou
| first1 = R
| title = RNA-based mechanisms regulating host-virus interactions
| journal = Immunological Reviews
| volume = 253
| issue = 1
| pages = 97–111
| last2 = Rana
| first2 = T. M.
| doi = 10.1111/imr.12053
}}</ref> In addition, the Espirito Santo virus (ESV) is defined as a sister species to DXV. This particular virus, ESV, was observed in an ''Aedes albopictus'' cell culture, which was obtained from a patient's serum infected with DENV-2. A difference between the ESV and CYV would be CYV's ability to independently replicate without on other viruses in insect cell culture.<ref name= marklewitz>{{Cite journal | doi = 10.1099/vir.0.045435-0| pmid = 22875257| title = First isolation of an Entomobirnavirus from free-living insects| journal = Journal of General Virology| volume = 93| issue = Pt 11| pages = 2431–2435| year = 2012| last1 = Marklewitz | first1 = M.| last2 = Gloza-Rausch | first2 = F.| last3 = Kurth | first3 = A.| last4 = Kummerer | first4 = B. M.| last5 = Drosten | first5 = C.| last6 = Junglen | first6 = S.| doi-access = free}}</ref> A non-AUG start codon in ORF5 has been shown in ''Drosophila'' and may regulate translation, which indicates its function in entomobirnavirus host in reactions.<ref name= marklewitz/> When ORF5 is expressed, it is thought to mediate ribosomal frameshifting.<ref name= marklewitz/> A heptanucleotide that is located upstream of ORF (1897UUUUUUA) is found in both ESV and DXV. Together with phylogenetic analysis and the location differences of nucleotide and amino acids between CYV and ESV, it has been shown that CYV and ESV is one sister species to DXV.<ref name= marklewitz/>

==Research==
Although widely used in the laboratory, DXV has never been found as a natural infection of ''Drosophila'', and was originally identified in laboratory cell culture. DXV can infect [[Biology:Drosophilidae|fruit flies]] of the genus ''[[Biology:Drosophila|Drosophila]]'' and is commonly used to study innate immunity in the common model organism ''[[Biology:Drosophila melanogaster|Drosophila melanogaster]]''. The virus is also often used to study [[Biology:RNA interference|RNA interference]] as a mechanism of viral immunity in ''Drosophila''.{{cn|date=October 2022}}

DXV was a contaminant that was isolated in infectious studies with a member of the ''Rhabdoviridae'' family, the Sigma virus.<ref name=Tsai/> Since then, DXV has been widely used in research and has significantly contributed to the current knowledge of insect specific immune system.<ref name=zambon>{{Cite journal
 | pmid = 15878994
| pmc = 1129099
| year = 2005
| last1 = Zambon
| first1 = R. A.
| title = The Toll pathway is important for an antiviral response in Drosophila
| journal = Proceedings of the National Academy of Sciences
| volume = 102
| issue = 20
| pages = 7257–62
| last2 = Nandakumar
| first2 = M
| last3 = Vakharia
| first3 = V. N.
| last4 = Wu
| first4 = L. P.
| doi = 10.1073/pnas.0409181102
| bibcode = 2005PNAS..102.7257Z
| doi-access = free
}}</ref> Infection studies with DXV has shed light on the innate immune response and [[Biology:RNA interference|RNA interference]] (RNAi) in ''Drosophila'' flies.<ref name= zambon/> Additionally, using DXV in Drosophila showed that RNAi is a major form of an antiviral effector mechanism.<ref name= marklewitz/> In regards to the Toll pathway in antiviral response, there is evidence to show this pathway inhibits DXV replication in ''Drosophila''.<ref>{{Cite journal
 | pmid = 21209287
| year = 2011
| last1 = Valanne
| first1 = S
| title = The Drosophila Toll signaling pathway
| journal = The Journal of Immunology
| volume = 186
| issue = 2
| pages = 649–56
| last2 = Wang
| first2 = J. H.
| last3 = Rämet
| first3 = M
| doi = 10.4049/jimmunol.1002302
| doi-access = free
}}</ref> Furthermore, findings from DXV research on ''Drosophila'' significantly influenced studies on the dengue virus (DENV) to learn more about its innate immune response toward infections.<ref name= marklewitz/> It has been shown that DENV is controlled by RNAi in ''Drosophila'' cells and studies revealed that DENV's interaction with RNAi are just as vital as siRNAs. Engineered transgenic ''[[Biology:Aedes aegypti|Aedes aegypti]]'' mosquitos were shown to have resistance (caused by an RNAi response) against DENV-2 infections.<ref>{{Cite journal
 | pmid = 16537508
| pmc = 1449670
| year = 2006
| last1 = Franz
| first1 = A. W.
| title = Engineering RNA interference-based resistance to dengue virus type 2 in genetically modified Aedes aegypti
| journal = Proceedings of the National Academy of Sciences
| volume = 103
| issue = 11
| pages = 4198–203
| last2 = Sanchez-Vargas
| first2 = I
| last3 = Adelman
| first3 = Z. N.
| last4 = Blair
| first4 = C. D.
| last5 = Beaty
| first5 = B. J.
| last6 = James
| first6 = A. A.
| last7 = Olson
| first7 = K. E.
| doi = 10.1073/pnas.0600479103
| bibcode = 2006PNAS..103.4198F
| doi-access = free
}}</ref>

==References==
{{Reflist}}

==External links==
* [https://www.ncbi.nlm.nih.gov/ICTVdb/ICTVdB/00.009.0.03.001.htm ICTVdB Management (2006). 00.009.0.03.001. Drosophila X virus]. In: ICTVdB—The Universal Virus Database, version 4. Büchen-Osmond, C. (Ed), Columbia University, New York, USA.
* Brun, G. & Plus, N. in The genetics and biology of Drosophila (eds. Ashburner, M. & Wright, T. R. F.) 625–702 (Academic Press, New York., 1980).

{{Taxonbar|from=Q772836}}

{{DEFAULTSORT:Drosophila X Virus}}
[[Category:Birnaviridae]]
[[Category:Drosophila|X virus]]

{{Sourceattribution|Drosophila X virus}}