Editing Rotavirus (section)

=== 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 protein|''nonstructural'' proteins]] (NSPs), that are only produced in cells infected by rotavirus. These are called [[NSP1 (rotavirus)|NSP1]], [[NSP2 (rotavirus)|NSP2]], [[NSP3 (rotavirus)|NSP3]], [[NSP4 (rotavirus)|NSP4]], [[NSP5 (rotavirus)|NSP5]] and [[NSP6 (rotavirus)|NSP6]].<ref name="pmid20684716" />

At least six of the twelve proteins [[coding region|encoded]] by the rotavirus genome bind [[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 [[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 [[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]] [[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 [[capping enzyme]] that catalyses the formation of the [[5' cap]] in the [[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 [[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 [[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 [[protease]] enzyme [[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]] ([[Lewis antigen system]], [[ABO blood group system]] and [[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 [[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 [[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 [[Immunity (medical)|immunity]] to infection.<ref name="pmid16913048" />

==== Nonstructural viral proteins ====
NSP1, the product of gene 5, is a [[nonstructural protein|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 [[interferon]] response, the part of the [[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 [[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 [[RNA-binding protein]] that accumulates in cytoplasmic inclusions ([[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, [[Jean Cohen|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 [[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 [[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 [[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 [[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 ([[base pair]]s) !! Protein !! [[UniProt]] !! Molecular weight [[Atomic mass unit|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 (60 [[trimers]])<ref name="pmid36996819">{{cite journal |vauthors=Shah PN, Gilchrist JB, Forsberg BO, Burt A, Howe A, Mosalaganti S, Wan W, Radecke J, Chaban Y, Sutton G, Stuart DI, Boyce M |title=Characterization of the rotavirus assembly pathway in situ using cryoelectron tomography |journal=Cell Host & Microbe |volume=31 |issue=4 |pages=604–615.e4 |date=April 2023 |pmid=36996819 |pmc=7615348 |doi=10.1016/j.chom.2023.03.004 |url=}}</ref>  || Cell attachment, virulence
|-
!5
| 1611 || [[NSP1 (rotavirus)|NSP1]] || {{UniProt|Q99FX5}} || 59 || Nonstructural || 0 || 5'RNA binding, interferon antagonist
|-
!6
| 1356 || VP6 || {{UniProt|Q6LE89}} || 45 || Inner Capsid || 780 (260 trimers)<ref name="pmid36996819"/>|| Structural and species-specific antigen
|-
!7
| 1104 || [[NSP3 (rotavirus)|NSP3]] || {{UniProt|P03536}} || 37 || Nonstructural || 0 || Enhances viral mRNA activity and shut-offs  cellular protein synthesis
|-
!8
| 1059 || [[NSP2 (rotavirus)|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 (260 trimers)<ref name="pmid36996819"/>  || Structural and neutralisation  antigen
|-
!10
| 751 || [[NSP4 (rotavirus)|NSP4]] || {{UniProt|P04512}} || 20 || Nonstructural || 0 || Viroporin ([[enterotoxin]])
|-
!11
| 667 || [[NSP5 (rotavirus)|NSP5]] [[NSP6 (rotavirus)|NSP6]] || {{UniProt|A2T3Q9}} {{UniProt|P11203}} || 22 || Nonstructural || 0 || ssRNA and dsRNA binding modulator of [[NSP2 (rotavirus)|NSP2]], phosphoprotein
|}
This table is based on the [[simian]] rotavirus strain SA11. RNA-protein coding assignments differ in some strains.