: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.{{cite web |title=Virus Taxonomy: 2024 Release |url=https://ictv.global/taxonomy |publisher=International Committee on Taxonomy of Viruses |access-date=22 April 2025}}{{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 }} Humans are primarily infected by rotaviruses in the species RVA. This one and the other species cause disease in other animals,{{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 }} for example, species RVH in pigs, RVD, RVF and RVG in birds, RVI in cats and RVJ in bats.{{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 }}{{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 }}{{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 }}{{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 }}

Within group A rotaviruses there are different strains, called serotypes.{{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 }} 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.{{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/ }} Because the two genes that determine G-types and P-types can be passed on separately to progeny viruses, different combinations are found. A whole genome genotyping system has been established for group A rotaviruses, which has been used to determine the origin of atypical strains.{{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 }} The prevalence of the individual G-types and P-types varies between, and within, countries and years.{{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}} There are at least 36 G types and 51 P types{{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 }} 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].{{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 }}

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.{{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}} The RNA is surrounded by a three-layered icosahedral protein capsid. Viral particles are up to 76.5{{nbsp}}nm in diameter{{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 }}{{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}} and are not enveloped.{{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 }}

File:Rotavirus Structure.png

There are six viral proteins (VPs) that form the virus particle (virion). These structural proteins are called VP1, VP2, VP3, VP4, VP6 and VP7. In addition to the VPs, there are six nonstructural proteins (NSPs), that are only produced in cells infected by rotavirus. These are called NSP1, NSP2, NSP3, NSP4, NSP5 and NSP6.

At least six of the twelve proteins encoded by the rotavirus genome bind RNA.{{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 }} 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 mRNA translation and regulation of gene expression.{{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}}

File:Rotavirus with gold- labelled monoclonal antibody.jpg 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.{{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 }} 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.{{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 }}

VP2 forms the core layer of the virion and binds the RNA genome.{{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}}

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.{{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}} The cap stabilises viral mRNA by protecting it from nucleic acid degrading enzymes called nucleases.{{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 }}

VP4 is on the surface of the virion that protrudes as a spike.{{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}} It binds to molecules on the surface of cells called receptors and drives the entry of the virus into the cell.{{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}} 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.{{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}} VP4 determines how virulent the virus is and it determines the P-type of the virus.{{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 }} 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.{{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 }} This resistance is dependent on the rotavirus genotype.{{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 }}

VP6 forms the bulk of the capsid. It is highly antigenic and can be used to identify rotavirus species. This protein is used in laboratory tests for rotavirus infections.{{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 }}

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 to infection.

NSP1, the product of gene 5, is a nonstructural RNA-binding protein.{{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 }} 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 IRF transcription factors required for interferon gene transcription.{{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 }}

NSP2 is an RNA-binding protein that accumulates in cytoplasmic inclusions (viroplasms) and is required for genome replication.{{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 }}

NSP3 is bound to viral mRNAs in infected cells and it is responsible for the shutdown of cellular protein synthesis.{{cite journal |title=Rotavirus protein NSP3 (NS34) is bound to the 3' end consensus sequence of viral mRNAs in infected cells

|journal=Journal of Virology |volume=67 |issue=6 |pages=3159–3165 |year=1993|pmid=8388495 |url=http://jvi.asm.org/cgi/reprint/67/6/3159 |format=PDF |pmc=237654 |vauthors=Poncet D, Aponte C, Cohen J|doi=10.1128/JVI.67.6.3159-3165.1993 }} 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.{{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 }} Efficient translation of rotavirus mRNA, which lacks the 3' poly(A) tail, does not require either of these factors.{{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}}

NSP4 is a viral enterotoxin that induces diarrhoea and was the first viral enterotoxin discovered.{{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 }} It is a viroporin that elevates cytosolic Ca²⁺ in mammalian cells.{{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=}}

NSP5 is encoded by genome segment 11 of rotavirus A. In virus-infected cells NSP5 accumulates in the viroplasm.{{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 }}

NSP6 is a nucleic acid binding protein{{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}} and is encoded by gene 11 from an out-of-phase open reading frame.{{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}}

This table is based on the simian rotavirus strain SA11. RNA-protein coding assignments differ in some strains.

File:Rotavirus replication.png

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. The virus enters cells by receptor mediated endocytosis and form a 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 concentration. This causes the breakdown of VP7 trimers into single protein subunits, leaving the VP2 and VP6 protein coats around the viral dsRNA, forming a double-layered particle (DLP).{{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}}

The eleven dsRNA strands remain within the protection of the two protein shells and the viral RNA-dependent RNA polymerase creates mRNA transcripts of the double-stranded viral genome. By remaining in the core, the viral RNA evades innate host immune responses including RNA interference that are triggered by the presence of double-stranded RNA.{{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 }}

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.{{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 }} 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 progeny viruses are released from the cell by lysis.{{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}}{{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 }}

File:Multiple rotavirus particles.jpg of an infected child|alt=Many rotavirus particles packed together, which all look similar]]

Rotaviruses are transmitted by the faecal–oral route, via contact with contaminated hands, surfaces and objects,{{cite journal

|vauthors=Butz AM, Fosarelli P, Dick J, Cusack T, Yolken R |title=Prevalence of rotavirus on high-risk fomites in day-care facilities

|journal=Pediatrics

|volume=92

|issue=2

|pages=202–205

|year=1993

|doi=10.1542/peds.92.2.202

|pmid=8393172

|s2cid=20327842

}} and possibly by the respiratory route.{{cite journal

|author=Dennehy PH

|s2cid=28625697

|title=Transmission of rotavirus and other enteric pathogens in the home

|journal=Pediatric Infectious Disease Journal

|volume=19

|issue=Suppl 10

|pages=S103–105

|year=2000

|pmid=11052397

|doi=10.1097/00006454-200010001-00003

|doi-access=free

}} Viral diarrhoea is highly contagious. The faeces of an infected person can contain more than 10 trillion infectious particles per gram; fewer than 100 of these are required to transmit infection to another person.{{cite journal |vauthors=Grimwood K, Lambert SB |s2cid=31164630 |title=Rotavirus vaccines: opportunities and challenges |journal=Human Vaccines |volume=5 |issue=2 |pages=57–69 |year=2009 |pmid=18838873 |doi=10.4161/hv.5.2.6924 |url=http://www.landesbioscience.com/journals/hv/abstract.php?id=6924|doi-access=free }}

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

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

Rotavirus infections can occur throughout life: the first usually produces symptoms, but subsequent infections are typically mild or asymptomatic,{{cite journal |vauthors=Glass RI, Parashar UD, Bresee JS, Turcios R, Fischer TK, Widdowson MA, Jiang B, Gentsch JR |s2cid=34569166 |title=Rotavirus vaccines: current prospects and future challenges |journal=The Lancet |volume=368 |issue=9532 |pages=323–332 |year= 2006 |pmid=16860702 |doi=10.1016/S0140-6736(06)68815-6 }}{{cite journal |vauthors=Bishop RF |title=Natural history of human rotavirus infection |journal=Archives of Virology. Supplementum |volume=12 |issue= |pages=119–28 |date=1996 |pmid=9015109 |doi=10.1007/978-3-7091-6553-9_14|isbn=978-3-211-82875-5 }} as the immune system provides some protection.{{cite book |author=Offit PA|title=Gastroenteritis viruses|isbn=978-0-471-49663-2 |publisher=Wiley |location=New York |year=2001 |pages=106–124}} Consequently, symptomatic infection rates are highest in children under two years of age and decrease progressively towards 45 years of age.{{cite book |vauthors=Ramsay M, Brown D |veditors=Desselberger U, Gray J |title=Rotaviruses: Methods and Protocols|series=Methods in Molecular Medicine|volume=34|pages=217–238 |publisher=Humana Press |location=Totowa, NJ |year=2000|isbn=978-0-89603-736-6|chapter=Epidemiology of Group A Rotaviruses: Surveillance and Burden of Disease Studies|doi=10.1385/1-59259-078-0:217|pmid=21318862}} The most severe symptoms tend to occur in children six months to two years of age, the elderly, and those with immunodeficiency. Due to immunity acquired in childhood, most adults are not susceptible to rotavirus; gastroenteritis in adults usually has a cause other than rotavirus, but asymptomatic infections in adults may maintain the transmission of infection in the community.{{cite journal |vauthors=Anderson EJ, Weber SG |title=Rotavirus infection in adults |journal=The Lancet Infectious Diseases |volume=4 |issue=2 |pages=91–99 |year=2004 |pmid=14871633 |doi=10.1016/S1473-3099(04)00928-4 |pmc=7106507 }} There is some evidence to suggest blood group can impact on the susceptibility to infection by rotaviruses.{{cite journal |vauthors=Elhabyan A, Elyaacoub S, Sanad E, Abukhadra A, Elhabyan A, Dinu V |title=The role of host genetics in susceptibility to severe viral infections in humans and insights into host genetics of severe COVID-19: A systematic review |journal=Virus Research |volume=289 |issue= |pages=198163 |date=November 2020 |pmid=32918943 |pmc=7480444 |doi=10.1016/j.virusres.2020.198163 }}

File:Rotavirus infected gut.jpg

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

The diarrhoea is caused by multiple activities of the virus.{{cite journal |vauthors=Ramig RF |title=Pathogenesis of intestinal and systemic rotavirus infection |journal=Journal of Virology |volume=78 |issue=19 |pages=10213–10220 |year=2004 |pmid=15367586 |pmc=516399 |doi=10.1128/JVI.78.19.10213-10220.2004 }} Malabsorption occurs because of the destruction of gut cells called enterocytes. The toxic rotavirus protein NSP4 induces age- and calcium ion-dependent chloride secretion, disrupts SGLT1 (sodium/glucose cotransporter 2) transporter-mediated reabsorption of water, apparently reduces activity of brush-border membrane disaccharidases, and activates the calcium ion-dependent secretory reflexes of the enteric nervous system. The elevated concentrations of calcium ions in the cytosol (which are required for the assembly of the progeny viruses) is achieved by NSP4 acting as a viroporin. This increase in calcium ions leads to autophagy (self destruction) of the infected enterocytes.{{cite journal |vauthors=Hyser JM, Collinson-Pautz MR, Utama B, Estes MK |title=Rotavirus disrupts calcium homeostasis by NSP4 viroporin activity |journal=mBio |volume=1 |issue=5 |year=2010 |pmid=21151776 |pmc=2999940 |doi=10.1128/mBio.00265-10 }}

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

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

Healthy enterocytes secrete lactase into the small intestine; milk intolerance due to lactase deficiency is a symptom of rotavirus infection,{{cite journal |author=Farnworth ER |title=The evidence to support health claims for probiotics |journal=The Journal of Nutrition |volume=138 |issue=6 |pages=1250S–1254S |year=2008 |pmid=18492865 |doi=10.1093/jn/138.6.1250S |doi-access=free }} which can persist for weeks.{{cite journal |vauthors=Ouwehand A, Vesterlund S |title=Health aspects of probiotics |journal=IDrugs: The Investigational Drugs Journal |volume=6 |issue=6 |pages=573–580 |year=2003 |pmid=12811680 }} A recurrence of mild diarrhoea often follows the reintroduction of milk into the child's diet, due to bacterial fermentation of the disaccharide lactose in the gut.{{cite journal

|author=Arya SC

|title=Rotaviral infection and intestinal lactase level

|journal=Journal of Infectious Diseases

|volume=150

|issue=5

|page=791

|year=1984

|pmid=6436397

|doi=10.1093/infdis/150.5.791

|doi-access=free

}}

Rotaviruses elicit both B and T cell immune responses. Antibodies to the rotavirus VP4 and VP7 proteins neutralise viral infectivity in vitro and in vivo.{{cite journal |vauthors=Ward R |title=Mechanisms of protection against rotavirus infection and disease |journal=The Pediatric Infectious Disease Journal |volume=28 |issue=Suppl 3 |pages=S57–S59 |year=2009 |pmid=19252425 |doi=10.1097/INF.0b013e3181967c16 |doi-access=free }} Specific antibodies of the classes IgM, IgA and IgG are produced, which have been shown to protect against rotavirus infection by the passive transfer of the antibodies in other animals.{{cite journal |vauthors=Vega CG, Bok M, Vlasova AN, Chattha KS, Fernández FM, Wigdorovitz A, Parreño VG, Saif LJ |title=IgY antibodies protect against human Rotavirus induced diarrhea in the neonatal gnotobiotic piglet disease model |journal=PLOS ONE |volume=7 |issue=8 |pages=e42788 |year=2012 |pmid=22880110 |pmc=3411843 |doi=10.1371/journal.pone.0042788 |bibcode=2012PLoSO...742788V |doi-access=free }} Maternal trans-placental IgG might play a role in the protection neonates from rotavirus infections, but on the other hand might reduce vaccine efficacy.{{cite journal |vauthors=Mwila K, Chilengi R, Simuyandi M, Permar SR, Becker-Dreps S |title=Contribution of Maternal Immunity to Decreased Rotavirus Vaccine Performance in Low- and Middle-Income Countries |journal=Clinical and Vaccine Immunology |volume=24 |issue=1 |year=2017 |pmid=27847365 |pmc=5216432 |doi=10.1128/CVI.00405-16 }}

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

The levels of IgG and IgA in the blood and IgA in the gut correlate with protection from infection.{{cite journal |vauthors=Offit PA |title=Rotaviruses: immunological determinants of protection against infection and disease |journal=Advances in Virus Research |volume=44 |issue= |pages=161–202 |date=1994 |pmid=7817873 |pmc=7130874 |doi=10.1016/s0065-3527(08)60329-2 |isbn=978-0-12-039844-7 }} Rotavirus specific serum IgG and IgA at high titres (e.g. >1:200) have been claimed to be protective and there is a significant correlation between IgA titres and rotavirus vaccine efficacy.{{cite journal |vauthors=Patel M, Glass RI, Jiang B, Santosham M, Lopman B, Parashar U |title=A systematic review of anti-rotavirus serum IgA antibody titer as a potential correlate of rotavirus vaccine efficacy |journal=The Journal of Infectious Diseases |volume=208 |issue=2 |pages=284–294 |year=2013 |pmid=23596320 |doi=10.1093/infdis/jit166 |doi-access=free }}

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

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

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

{{Main|Rotavirus vaccine}}

Rotaviruses are highly contagious and cannot be treated with antibiotics or other drugs. Because improved sanitation does not decrease the prevalence of rotaviral disease, and the rate of hospitalisations remains high despite the use of oral rehydrating medicines, the primary public health intervention is vaccination.{{cite journal |author=Bernstein DI |title=Rotavirus overview |journal=The Pediatric Infectious Disease Journal |volume=28 |issue= Suppl 3|pages=S50–S53 |year= 2009 |pmid=19252423 |doi=10.1097/INF.0b013e3181967bee |s2cid=30544613 |doi-access=free }} In 1998, a rotavirus vaccine was licensed for use in the United States. Clinical trials in the United States, Finland, and Venezuela had found it to be 80–100% effective at preventing severe diarrhoea caused by rotavirus A, and researchers had detected no statistically significant serious adverse effects.{{cite journal |title=Rotavirus vaccine for the prevention of rotavirus gastroenteritis among children. Recommendations of the Advisory Committee on Immunization Practices (ACIP) |journal=MMWR. Recommendations and Reports |volume=48 |issue=RR-2 |pages=1–20 |year=1999 |pmid=10219046 }}{{cite book

|author=Kapikian AZ

|title=Gastroenteritis Viruses

|chapter=A rotavirus vaccine for prevention of severe diarrhoea of infants and young children: development, utilization and withdrawal

|volume=238

|pages=153–171; discussion 171–179

|year=2001

|pmid=11444025

|doi=10.1002/0470846534.ch10

|series=Novartis Foundation Symposia

|isbn=978-0-470-84653-7

}} The manufacturer, however, withdrew it from the market in 1999, after it was discovered that the vaccine may have contributed to an increased risk for intussusception, a type of bowel obstruction, in one of every 12,000 vaccinated infants.{{cite journal |author=Bines |first=JE |author-link=Julie Bines |year=2005 |title=Rotavirus vaccines and intussusception risk |url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0267-1379&volume=21&issue=1&spage=20 |journal=Current Opinion in Gastroenterology |volume=21 |issue=1 |pages=20–25 |pmid=15687880 |access-date=21 January 2008 |archive-date=11 May 2013 |archive-url=https://web.archive.org/web/20130511014221/http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0267-1379&volume=21&issue=1&spage=20 |url-status=dead }} The experience provoked intense debate about the relative risks and benefits of a rotavirus vaccine.{{cite journal |author=Bines J |title=Intussusception and rotavirus vaccines |journal=Vaccine |volume=24 |issue=18 |pages=3772–3776 |year=2006 |pmid=16099078 |doi=10.1016/j.vaccine.2005.07.031}}

In 2006, two new vaccines against {{nowrap|rotavirus A}} infection were shown to be safe and effective in children,{{cite journal

|author=Dennehy PH

|title=Rotavirus vaccines: an overview

|journal=Clinical Microbiology Reviews

|volume=21

|issue=1

|pages=198–208

|year=2008

|pmid=18202442

|doi=10.1128/CMR.00029-07

|pmc=2223838

}} and in 2009, the WHO recommended that rotavirus vaccine be included in all national immunisation programmes.{{cite journal |vauthors=Tate JE, Patel MM, Steele AD, Gentsch JR, Payne DC, Cortese MM, Nakagomi O, Cunliffe NA, Jiang B, Neuzil KM, de Oliveira LH, Glass RI, Parashar UD |s2cid=28963507 |title=Global impact of rotavirus vaccines |journal=Expert Review of Vaccines |volume=9 |issue=4 |pages=395–407 |year= 2010 |pmid=20370550 |doi=10.1586/erv.10.17}}

The incidence and severity of rotavirus infections has declined significantly in countries that have acted on this recommendation.{{cite journal |vauthors=Giaquinto C, Dominiak-Felden G, Van Damme P, Myint TT, Maldonado YA, Spoulou V, Mast TC, Staat MA |s2cid=23996836 |title=Summary of effectiveness and impact of rotavirus vaccination with the oral pentavalent rotavirus vaccine: a systematic review of the experience in industrialized countries |journal=Human Vaccines |volume=7 |issue=7 |pages=734–748 |year =2011 |pmid=21734466 |doi=10.4161/hv.7.7.15511 |url=http://www.landesbioscience.com/journals/hv/abstract.php?id=15511|doi-access=free }} A 2014 review of available clinical trial data from countries routinely using rotavirus vaccines in their national immunisation programs found that rotavirus vaccines have reduced rotavirus hospitalisations by 49–92% and all cause diarrhoea hospitalisations by 17–55%.{{Cite journal|vauthors=Tate JE, Parashar UD|date=2014|title=Rotavirus Vaccines in Routine Use|journal=Clinical Infectious Diseases|volume=59|issue=9|pages=1291–1301|doi=10.1093/cid/ciu564|pmid=25048849|doi-access=free|pmc=11980788}} In Mexico, which in 2006 was among the first countries in the world to introduce rotavirus vaccine, diarrhoeal disease death rates dropped during the 2009 rotavirus season by more than 65 percent among children age two and under.{{cite journal|vauthors=Richardson V, Hernandez-Pichardo J, Quintanar-Solares M, Esparza-Aguilar M, Johnson B, Gomez-Altamirano CM, Parashar U, Patel M |s2cid=27287753|title=Effect of Rotavirus Vaccination on Death From Childhood Diarrhea in Mexico|journal=The New England Journal of Medicine|year=2010|volume=362|issue=4|pages=299–305|doi=10.1056/NEJMoa0905211|pmid=20107215|display-authors=2|doi-access=free}} In Nicaragua, which in 2006 became the first developing country to introduce a rotavirus vaccine, severe rotavirus infections were reduced by 40 percent and emergency room visits by a half.{{cite journal |vauthors=Patel M, Pedreira C, De Oliveira LH, Umaña J, Tate J, Lopman B, Sanchez E, Reyes M, Mercado J, Gonzalez A, Perez MC, Balmaceda A, Andrus J, Parashar U |s2cid=7723807 |title=Duration of protection of pentavalent rotavirus vaccination in Nicaragua |journal=Pediatrics |volume=130 |issue=2 |pages=e365–e372 |year=2012 |pmid=22753550 |doi=10.1542/peds.2011-3478 }} In the United States, rotavirus vaccination since 2006 has led to drops in rotavirus-related hospitalisations by as much as 86 percent.{{cite journal |vauthors=Omatola CA, Olaniran AO |title=Rotaviruses: From Pathogenesis to Disease Control-A Critical Review |journal=Viruses |volume=14 |issue=5 |date=April 2022 |page=875 |pmid=35632617 |pmc=9143449 |doi=10.3390/v14050875|doi-access=free }} The vaccines may also have prevented illness in non-vaccinated children by limiting the number of circulating infections.{{cite journal|vauthors=Patel MM, Parashar UD, etal |title=Real World Impact of Rotavirus Vaccination|journal=Pediatric Infectious Disease Journal|year=2011|volume=30|issue=1|doi=10.1097/INF.0b013e3181fefa1f|pages=S1–S5|pmid=21183833|s2cid=1893099 |doi-access=free}} In developing countries in Africa and Asia, where the majority of rotavirus deaths occur, a large number of safety and efficacy trials as well as recent post-introduction impact and effectiveness studies of Rotarix and RotaTeq have found that vaccines dramatically reduced severe disease among infants.{{Cite journal|date=2010|veditors=Steele AD, Armah GE, Page NA, Cunliffe NA|title=Rotavirus Infection in Africa: Epidemiology, Burden of Disease, and Strain Diversity|journal=Journal of Infectious Diseases|volume=202|issue=Suppl 1|pages=S1–S265|doi=10.1086/653545|pmid=20684687|vauthors=Neuzil KM, Armah GE, Parashar UD, Steele AD |doi-access=free}}{{Cite journal|date=2009|veditors=Nelson EA, Widdowson MA, Kilgore PE, Steele D, Parashar UD|title=Rotavirus in Asia: Updates on Disease Burden, Genotypes and Vaccine Introduction|url=http://www.sciencedirect.com/science/journal/0264410X/27/supp/S5|journal=Vaccine|volume=27|issue=Suppl 5|pages=F1–F138}}{{cite journal|author=World Health Organization|title=Rotavirus vaccines: an update|journal=Weekly Epidemiological Record|year= 2009|volume=51–52|issue=84|pages=533–540|url=https://www.who.int/wer/2009/wer8451_52.pdf|access-date=8 May 2012}} In September 2013, the vaccine was offered to all children in the UK, aged between two and three months.{{cite web|url=http://www.dh.gov.uk/health/2012/11/rotavirus/ |title= New vaccine to help protect babies against rotavirus|publisher=UK Department of Health|date=10 November 2012 |access-date= 10 November 2012}} A 2022 study found that the number of rotavirus cases in infants in England under one year of age was reduced by 77–88%. In all age groups, the number of laboratory-confirmed rotavirus infections was reduced by 69–83%.{{cite journal |vauthors=Gower CM, Stowe J, Andrews NJ, Dunning J, Ramsay ME, Ladhani SN |title=Sustained Declines in Age Group-Specific Rotavirus Infection and Acute Gastroenteritis in Vaccinated and Unvaccinated Individuals During the 5 Years Since Rotavirus Vaccine Introduction in England |journal=Clinical Infectious Diseases |volume=74 |issue=3 |pages=437–445 |date=February 2022 |pmid=34043765 |doi=10.1093/cid/ciab460}} In Europe, hospitalisation rates following infection by rotaviruses have decreased by 65% to 84% following the introduction of the vaccine.{{cite journal |vauthors=Karafillakis E, Hassounah S, Atchison C |title=Effectiveness and impact of rotavirus vaccines in Europe, 2006–2014 |journal=Vaccine |volume=33 |issue=18 |pages=2097–2107 |year=2015 |pmid=25795258 |doi=10.1016/j.vaccine.2015.03.016 |doi-access=free }} Globally, vaccination has reduced hospital admissions and emergency department visits by a median of 67%.{{cite journal |vauthors=Burnett E, Jonesteller CL, Tate JE, Yen C, Parashar UD |title=Global Impact of Rotavirus Vaccination on Childhood Hospitalizations and Mortality from Diarrhea |journal=The Journal of Infectious Diseases |volume=215 |issue=11 |pages=1666–1672 |year=2017 |pmid=28430997 |doi=10.1093/infdis/jix186 |pmc=5543929}}

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

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

Rotavirus A, which accounts for more than 90% of rotavirus gastroenteritis in humans,{{cite journal |vauthors=Leung AK, Kellner JD, Davies HD |s2cid=39847059 |title=Rotavirus gastroenteritis |journal=Advances in Therapy |volume=22 |issue=5 |pages=476–487 |year=2005 |pmid=16418157 |doi=10.1007/BF02849868 }} is endemic worldwide. Each year rotaviruses cause millions of cases of diarrhoea in developing countries, almost 2{{nbsp}}million of which result in hospitalisation. In 2019, an estimated 151,714 children younger than five died from rotavirus infections, 90 percent of whom were in developing countries. Almost every child has been infected with rotaviruses by age five.{{cite journal

|vauthors=Parashar UD, Gibson CJ, Bresse JS, Glass RI |title=Rotavirus and severe childhood diarrhea

|journal=Emerging Infectious Diseases

|volume=12

|issue=2

|pages=304–306

|year=2006

|pmid=16494759

|doi=10.3201/eid1202.050006

|pmc=3373114

}} Rotaviruses are the leading single cause of severe diarrhoea among infants and children, are responsible for about a third of the cases requiring hospitalisation, and cause 37% of deaths attributable to diarrhoea and 5% of all deaths in children younger than five.{{cite journal|year= 2012|title=2008 estimate of worldwide rotavirus-associated mortality in children younger than 5 years before the introduction of universal rotavirus vaccination programmes: a systematic review and meta-analysis|journal=The Lancet Infectious Diseases|volume=12|issue=2|pages=136–141|doi=10.1016/S1473-3099(11)70253-5|pmid=22030330|vauthors=Tate JE, Burton AH, Boschi-Pinto C, Steele AD, Duque J, Parashar UD|url=https://zenodo.org/record/1260248}} Boys are twice as likely as girls to be admitted to hospital for rotavirus infections.{{cite journal |vauthors=Rheingans RD, Heylen J, Giaquinto C |s2cid=3272810 |title=Economics of rotavirus gastroenteritis and vaccination in Europe: what makes sense? |journal=Pediatric Infectious Disease Journal |volume=25 |issue= Suppl 1|pages=S48–S55 |year=2006 |pmid=16397429 |doi=10.1097/01.inf.0000197566.47750.3d|doi-access=free }}{{cite journal |vauthors=Ryan MJ, Ramsay M, Brown D, Gay NJ, Farrington CP, Wall PG |title=Hospital admissions attributable to rotavirus infection in England and Wales |journal=Journal of Infectious Diseases |volume=174 |issue=Suppl 1 |pages=S12–S18 |year=1996 |pmid=8752285 |doi=10.1093/infdis/174.Supplement_1.S12|doi-access=free }} In the pre-vaccination era, rotavirus infections occurred primarily during cool, dry seasons.{{cite journal |vauthors=Atchison CJ, Tam CC, Hajat S, van Pelt W, Cowden JM, Lopman BA |title=Temperature-dependent transmission of rotavirus in Great Britain and The Netherlands |journal=Proceedings of the Royal Society B: Biological Sciences |volume=277 |issue=1683 |pages=933–942 |year=2010 |pmid=19939844 |pmc=2842727 |doi=10.1098/rspb.2009.1755}}{{cite journal |vauthors=Levy K, Hubbard AE, Eisenberg JN |title=Seasonality of rotavirus disease in the tropics: a systematic review and meta-analysis |journal=International Journal of Epidemiology |volume=38 |issue=6 |pages=1487–1496 |year= 2009 |pmid=19056806 |pmc=2800782 |doi=10.1093/ije/dyn260 }} The number attributable to food contamination is unknown.{{cite journal |vauthors=Koopmans M, Brown D |title=Seasonality and diversity of Group A rotaviruses in Europe |journal=Acta Paediatrica |volume=88 |issue=Suppl 426 |pages=14–19 |year=1999 |pmid=10088906 |doi=10.1111/j.1651-2227.1999.tb14320.x|s2cid=10969637 }}

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

Rotavirus B, also called adult diarrhoea rotavirus or ADRV, has caused major epidemics of severe diarrhoea affecting thousands of people of all ages in China. These epidemics occurred as a result of sewage contamination of drinking water.{{cite journal |vauthors=Hung T, Wang C, Fang Z, Chou Z, Chang X, Liong X, Chen G, Yao H, Chao T, Ye W, Den S, Chang W |title=Waterborne outbreak of rotavirus diarrhea in adults in China caused by a novel rotavirus |journal=The Lancet |volume=323 |issue=8387 |pages=1139–1142 |year=1984 |pmid=6144874 | doi = 10.1016/S0140-6736(84)91391-6|s2cid=54346351 }}{{cite journal |vauthors=Fang ZY, Ye Q, Ho MS, Dong H, Qing S, Penaranda ME, Hung T, Wen L, Glass RI |title=Investigation of an outbreak of adult diarrhea rotavirus in China |journal=Journal of Infectious Diseases |volume=160 |issue=6 |pages=948–953 |year=1989 |pmid=2555422 |doi=10.1093/infdis/160.6.948}} Rotavirus B infections also occurred in India in 1998; the causative strain was named CAL. Unlike ADRV, the CAL strain is endemic.{{cite journal |vauthors=Kelkar SD, Zade JK |title=Group B rotaviruses similar to strain CAL-1, have been circulating in Western India since 1993 |journal=Epidemiology and Infection |volume=132 |issue=4 |pages=745–749 |year=2004 |pmid=15310177 |pmc=2870156 |doi=10.1017/S0950268804002171 | s2cid = 34463384}}{{cite journal |vauthors=Ahmed MU, Kobayashi N, Wakuda M, Sanekata T, Taniguchi K, Kader A, Naik TN, Ishino M, Alam MM, Kojima K, Mise K, Sumi A |title=Genetic analysis of group B human rotaviruses detected in Bangladesh in 2000 and 2001 |journal=Journal of Medical Virology |volume=72 |issue=1 |pages=149–155 |year=2004 |pmid=14635024 |doi=10.1002/jmv.10546|s2cid=21258083 }} To date, epidemics caused by rotavirus B have been confined to mainland China, and surveys indicate a lack of immunity to this species in the United States.{{cite journal |vauthors=Penaranda ME, Ho MS, Fang ZY, Dong H, Bai XS, Duan SC, Ye WW, Estes MK, Echeverria P, Hung T |title=Seroepidemiology of adult diarrhea rotavirus in China, 1977 to 1987 |journal=Journal of Clinical Microbiology |volume=27 |issue=10 |pages=2180–2183 |year=1989 |pmid=2479654 |pmc=266989 |doi= 10.1128/JCM.27.10.2180-2183.1989}} Rotavirus C has been associated with rare and sporadic cases of diarrhoea in children, and small outbreaks have occurred in families.{{cite journal |vauthors=Moon S, Humphrey CD, Kim JS, Baek LJ, Song JW, Song KJ, Jiang B |title=First detection of group C rotavirus in children with acute gastroenteritis in South Korea |journal=Clinical Microbiology and Infection |volume=17 |issue=2 |pages=244–247 |year=2011 |pmid=20491826 |doi=10.1111/j.1469-0691.2010.03270.x |doi-access=free }}

File:Rotavirus seasonal distribution.png|The seasonal variation of rotavirus A infections in England: rates of infection peak during the winter months.{{Cite web|url=https://www.gov.uk/government/collections/rotavirus-vaccination-progarmme-for-infants|title=Rotavirus vaccination programme for infants|website=www.gov.uk|publisher=Public Health England|date=26 July 2013}}

File:Avertable-deaths-from-rotavirus-with-full-vaccine-coverage.png|Preventable child deaths from rotavirus vaccination, 2016. Annual number of preventable deaths in children under five years old from rotavirus if full coverage of the rotavirus vaccine was achieved.{{cite journal|url=https://ourworldindata.org/rotavirus-vaccine|title=Rotavirus vaccine – an effective tool that prevents children dying from diarrhea|vauthors=Dadonaite B, Ritchie H|journal=Our World in Data |year=2019}}

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

File:Flewett Rotavirus.jpg

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

In 1974, Thomas Henry Flewett suggested the name rotavirus after observing that, when viewed through an electron microscope, a rotavirus particle looks like a wheel ({{lang|la|rota}} in Latin){{cite journal |vauthors=Flewett TH, Bryden AS, Davies H, Woode GN, Bridger JC, Derrick JM |title=Relation between viruses from acute gastroenteritis of children and newborn calves |journal=The Lancet |volume=304 |issue=7872 |pages=61–63 |year=1974 |pmid=4137164 |doi=10.1016/S0140-6736(74)91631-6}} the name was officially recognised by the International Committee on Taxonomy of Viruses four years later.{{cite journal |author=Matthews RE |title=Third report of the International Committee on Taxonomy of Viruses. Classification and nomenclature of viruses |journal=Intervirology |volume=12 |issue=3–5 |pages=129–296 |year=1979 |pmid=43850 |doi=10.1159/000149081|doi-access=free }} In 1976, related viruses were described in several other species of animals. These viruses, all causing acute gastroenteritis, were recognised as a collective pathogen affecting humans and other animals worldwide.{{cite journal |vauthors=Flewett TH, Woode GN |title=The rotaviruses |journal=Archives of Virology |volume=57 |issue=1 |pages=1–23 |year=1978 |pmid=77663 |doi=10.1007/BF01315633 |pmc=7087197 }} Rotavirus serotypes were first described in 1980,{{cite journal |vauthors=Beards GM, Brown DW |s2cid=11547573 |title=The antigenic diversity of rotaviruses: significance to epidemiology and vaccine strategies |journal=European Journal of Epidemiology |volume=4 |issue=1 |pages=1–11 |year= 1988 |pmid=2833405 |doi=10.1007/BF00152685}} and in the following year, rotaviruses from humans were first grown in cell cultures derived from monkey kidneys, by adding trypsin (an enzyme found in the duodenum of mammals and now known to be essential for rotavirus to replicate) to the culture medium.{{cite journal |vauthors=Urasawa T, Urasawa S, Taniguchi K |title=Sequential passages of human rotavirus in MA-104 cells |journal=Microbiology and Immunology |volume=25 |issue=10 |pages=1025–1035 |year=1981 |pmid=6273696 |doi=10.1111/j.1348-0421.1981.tb00109.x |s2cid=25276891 |doi-access=free }} The ability to grow rotaviruses in culture accelerated the pace of research, and by the mid-1980s the first candidate vaccines were being evaluated.{{cite journal |vauthors=Ward RL, Bernstein DI |title=Rotarix: a rotavirus vaccine for the world |journal=Clinical Infectious Diseases |volume=48 |issue=2 |pages=222–228 |year =2009 |pmid=19072246 |doi=10.1086/595702 |doi-access=free }}

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