Editing Rotavirus (section)

== Virology ==

=== Types of rotavirus ===
There are 11 species of rotavirus (sometimes informally called ''groups'') referred to as RVA, RVB, RVC, RVD, RVF, RVG, RVH, RVI, RVJ, RVK and RVL.<ref>{{cite web |title=Virus Taxonomy: 2024 Release |url=https://ictv.global/taxonomy |publisher=International Committee on Taxonomy of Viruses |access-date=22 April 2025}}</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 rotaviruses in the species RVA. This one and the other 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 | issue = Suppl 1 | pages = S43–48 | date = September 2010 | pmid = 20684716 | doi = 10.1086/653548 | doi-access = free }}</ref> for example, species RVH in pigs, RVD, RVF and RVG in birds, RVI in cats and RVJ 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 |bibcode=2017InfGE..48...19B }}</ref>

Within group A  rotaviruses there are different strains, called [[serovar|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 [[influenza]] virus, a dual classification system is used based on two proteins on the surface of the virus. The [[glycoprotein]] VP7 defines the G serotypes and the [[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 group A rotaviruses, 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 [[genome]] of rotaviruses consists of 11 unique double helix molecules of [[RNA]] (dsRNA) which are 18,555 nucleotides in total. Each helix, or segment, is a [[gene]], numbered 1 to 11 by decreasing size. Each gene codes for one [[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 [[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}}</ref> and are not [[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 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.

=== 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 [[endocytosis|receptor mediated endocytosis]] and form a [[Vesicle (biology)|vesicle]] known as an [[endosome]]. Proteins in the third layer (VP7 and the VP4 spike) disrupt the membrane of the endosome, creating a difference in the [[Calcium in biology|calcium]] concentration. This causes the breakdown of VP7 [[Trimer (biochemistry)|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 replicase|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 [[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 [[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 [[Offspring|progeny]] viruses are released from the cell by [[cell lysis|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>