Rotavirus
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2008-06-26T15:08:12Z
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{{Taxobox
| name = Rotavirus
| status =
| status_ref =
| image = rotavirus.jpg
| image_width = 180px
| image_caption = Electron micrograph of Rotaviruses. The bar = 100 nm
| image2 =
| image2_width =
| image2_caption =
| virus_group = iii
| familia = [[Reoviridae]]
| genus = '''''Rotavirus'''''
| species = '''''A, B, C, D, E, F & G'''''
| baltimore Group = III
| binomial_authority =
| range_map_width =
| range_map_caption =
}}
{{DiseaseDisorder infobox|right |
Name = Rotaviral Gastroenteritis |
ICD10 = {{ICD10|A|08|0|a|00}}|
ICD9 = {{ICD9|008.61}} |
ICDO = |
Image = |
Caption = |
OMIM = |
MedlinePlus = 000252 |
eMedicineSubj = emerg |
eMedicineTopic = 401 |
eMedicine_mult = |
DiseasesDB = 11667 |
MeshID = D012401|
}}
'''Rotavirus''' is a [[genus]] of [[double-stranded RNA virus]] in the [[family (biology)|family]] [[Reoviridae]]. It is the leading cause of [[Diarrhea|severe diarrhoea]] among infants and young children.<ref name="pmid11052397"/> By the age of five, nearly every child in the world has been infected with rotavirus at least once.<ref name="pmid8793926"/> However, with each infection, [[immunity]] develops, subsequent infections are less severe,<ref name="pmid2849961"/> and adults are rarely affected.<ref name="pmid9015109"/> There are seven [[species]] of this virus, referred to as A, B, C, D, E, F and G. Rotavirus A, the most common, causes more than 90% of infections in humans.
Rotavirus is transmitted by the [[fecal-oral route|faecal-oral route]]. It infects [[enterocyte|cells]] that line the [[small intestine]] and produces an [[enterotoxin]], which induces [[gastroenteritis]], leading to severe diarrhoea and sometimes death through [[dehydration]]. Although rotavirus was discovered in 1973<ref name="pmid4127639"/> and accounts for up to 50% of hospitalisations for severe diarrhoea in infants and children,<ref name="pmid16397429"/> its importance is still not widely known within the [[public health]] community, particularly in [[developing country|developing countries]].<ref name="pmid17919334"/> In addition to its impact on human health, rotavirus also infects animals, and is a [[pathogen]] of livestock.<ref name="pmid2224836"/>
In developing countries, around 611,000 children under five years of age die from rotavirus infection each year,<ref name="pmid16494759"/> and almost two million more become severely ill.<ref name="pmid17919334"/> In the United States, rotavirus causes about 2.7 million cases of severe gastroenteritis in children, almost 60,000 hospitalisations, and around 37 deaths each year.<ref name="pmid17357047"/> Public health campaigns to combat rotavirus focus on providing [[oral rehydration therapy]] for infected children and [[vaccination]] to prevent the disease.<ref name="pmid18026034"/>
==History==
[[Image:Flewett Rotavirus.jpg|right|thumb|One of Flewett's original electron micrographs]]
[[Image:Rotavirus Reconstruction.jpg|right|thumb|Computer reconstruction of a rotavirus particle]]
In 1943, Jacob Light and Horace Hodes proved that a [[Filter (chemistry)|filterable]] agent, in the faeces of children with infectious diarrhoea, also caused scours (livestock diarrhoea) in cattle.<ref name="pmid18015921">{{cite journal |author=Light JS, Hodes HL |title=Studies on epidemic diarrhea of the new-born: Isolation of a Filtrable Agent Causing Diarrhea in Calves |journal=Am. J. Public Health Nations Health |volume=33 |issue=12 |pages=1451–1454 |year=1943 |pmid=18015921 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1527675}}</ref> Three decades later, preserved samples of the agent were shown to be rotavirus.<ref name="pmid184047">{{cite journal
|author=Mebus CA, Wyatt RG, Sharpee RL, ''et al''
|title=Diarrhea in gnotobiotic calves caused by the reovirus-like agent of human infantile gastroenteritis
|journal=Infect. Immun.
|volume=14
|issue=2
|pages=471–4
|year=1976
|pmid=184047
|url=http://iai.asm.org/cgi/reprint/14/2/471
|format=PDF
}}</ref> In the intervening years, a virus in mice<ref name="pmid4998842">
{{cite journal
|author=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=442–45
|year=1971
|pmid=4998842
}}</ref> was shown to be related to the virus causing scours.<ref name="pmid965097">
{{cite journal
|author=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=Infect. Immun.
|volume=14
|issue=3
|pages=804–10
|year=1976
|pmid=965097
|url=http://iai.asm.org/cgi/reprint/14/3/804
|format=PDF
}}</ref> In 1973, related viruses were described by [[Ruth Bishop]] in children with gastroenteritis, in Australia.<ref name="pmid4127639">
{{cite journal
|author=Bishop RF, Davidson GP, Holmes IH, Ruck BJ
|title=Virus particles in epithelial cells of duodenal mucosa from children with acute non-bacterial gastroenteritis
|journal=Lancet
|volume=2
|issue=7841
|pages=1281–3
|year=1973
|pmid=4127639
|doi=10.1016/S0140-6736(73)92867-5
}}</ref><ref name="pmid4742237">
{{cite journal
|author=Bishop RF, Davidson GP, Holmes IH, Ruck BJ |title=Letter: Evidence for viral gastroenteritis
|journal=N. Engl. J. Med.
|volume=289
|issue=20
|pages=1096–7
|year=1973
|pmid=4742237
}}</ref>
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 (''rota'' in Latin);<ref name="pmid77663"/><ref name="pmid4137164">{{cite journal
|author=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=Lancet
|volume=2
|issue=7872
|pages=61–3
|year=1974
|pmid=4137164
|doi=10.1016/S0140-6736(74)91631-6
}}</ref> the name was officially recognised by the [[International Committee on Taxonomy of Viruses]] four years later.<ref name="pmid43850">{{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
}}</ref> In 1976, related viruses were described in several other species of animals.<ref name="pmid965097">
{{cite journal
|author=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 of children, calves, piglets, mice, and foals
|journal=Infect. Immun.
|volume=14
|issue=3
|pages=804–10
|year=1976
|pmid=965097
}}</ref> These viruses, all causing acute gastroenteritis, were recognised as a collective pathogen affecting humans and animals worldwide.<ref name="pmid77663">
{{cite journal
|author=Flewett TH, Woode GN |title=The rotaviruses
|journal=Arch. Virol.
|volume=57
|issue=1
|pages=1–23
|year=1978
|pmid=77663 |doi=10.1007/BF01315633
}}</ref> Rotavirus serotypes were first described in 1980,<ref name="pmid6262451">
{{cite journal
|author=Beards GM, Pilfold JN, Thouless ME, Flewett TH
|title=Rotavirus serotypes by serum neutralisation
|journal=J. Med. Virol.
|volume=5
|issue=3
|pages=231–7
|year=1980
|pmid=6262451
|doi=10.1002/jmv.1890050307
}}</ref> and in the following year, rotavirus from humans was first grown in [[cell culture]]s derived from monkey kidneys, by adding [[trypsin]], (an enzyme found in the [[duodenum]] of [[mammals]] and is now known to be essential for rotavirus to replicate), to the culture medium.<ref>
{{cite journal
|author=Urasawa T, Urasawa S, Taniguchi K
|title=Sequential passages of human rotavirus in MA-104 cells
|journal=Microbiol. Immunol.
|volume=25
|issue=10
|pages=1025–35
|year=1981
|pmid=6273696
}} </ref> The ability to grow rotavirus in culture accelerated the pace of research, and by the mid-1980s the first candidate vaccines were being evaluated.<ref>
{{cite journal
|author=Vesikari T, Isolauri E, Delem A, ''et al''
|title=Clinical efficacy of the RIT 4237 live attenuated bovine rotavirus vaccine in infants vaccinated before a rotavirus epidemic
|journal=J. Pediatr.
|volume=107
|issue=2
|pages=189–94
|year=1985
|pmid=3894608
|doi=10.1016/S0022-3476(85)80123-2
}}</ref>
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 to 100% effective at preventing severe diarrhoea caused by rotavirus A, and researchers had detected no [[statistical significance|statistically significant]] serious [[adverse drug reaction|adverse effects]].<ref name="pmid10219046">{{cite journal
|author=
|title=Rotavirus vaccine for the prevention of rotavirus gastroenteritis among children. Recommendations of the Advisory Committee on Immunization Practices (ACIP)
|journal=MMWR Recomm Rep
|volume=48
|issue=RR-2
|pages=1–20
|year=1999
|pmid=10219046
}}</ref><ref name="pmid11444025">{{cite journal
|author=Kapikian AZ
|title=A rotavirus vaccine for prevention of severe diarrhoea of infants and young children: development, utilization and withdrawal
|journal=Novartis Found. Symp.
|volume=238
|pages=153–71; discussion 171–9
|year=2001
|pmid=11444025
}}</ref> 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 (medical disorder)|intussusception]], a type of [[bowel obstruction]], in one of every 12,000 vaccinated infants.<ref name="pmid15687880">{{cite journal
|author=Bines JE
|title=Rotavirus vaccines and intussusception risk
|journal=Curr. Opin. Gastroenterol.
|volume=21
|issue=1
|pages=20–5
|year=2005
|pmid=15687880
|url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0267-1379&volume=21&issue=1&spage=20
}}</ref> The experience provoked intense debate about the relative risks and benefits of a rotavirus vaccine.<ref name="pmid16099078">{{cite journal |author=Bines J |title=Intussusception and rotavirus vaccines |journal=Vaccine |volume=24 |issue=18 |pages=3772–6 |year=2006 |pmid=16099078 |doi=10.1016/j.vaccine.2005.07.031}}</ref>
In 2006, two new vaccines against {{nowrap|rotavirus A}} infection were shown to be safe and effective in children.<ref name="pmid18202442">{{cite journal
|author=Dennehy PH
|title=Rotavirus vaccines: an overview
|journal=Clin. Microbiol. Rev.
|volume=21
|issue=1
|pages=198–208
|year=2008
|pmid=18202442
|doi=10.1128/CMR.00029-07
|url=http://cmr.asm.org/cgi/pmidlookup?view=long&pmid=18202442
}}</ref>
==Signs and symptoms==
Rotavirus gastroenteritis is a mild to severe disease characterised by [[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.<ref name="pmid10532018">{{cite journal
|author=Hochwald C, Kivela L
|title=Rotavirus vaccine, live, oral, tetravalent (RotaShield)
|journal=Pediatr. Nurs.
|volume=25
|issue=2
|pages=203–4, 207
|year=1999
|pmid=10532018
}}</ref> 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.<ref name="pmid1962726">{{cite journal
|author=Maldonado YA, Yolken RH
|title=Rotavirus
|journal=Baillieres Clin. Gastroenterol.
|volume=4
|issue=3
|pages=609–25
|year=1990
|pmid=1962726
|doi=10.1016/0950-3528(90)90052-I
}}</ref>
Rotavirus A infections can occur throughout life: the first usually [[symptomatic|produces symptoms]], but subsequent infections are typically [[asymptomatic]],<ref name="pmid9015109">{{cite journal
|author=Bishop RF
|title=Natural history of human rotavirus infection
|journal=Arch. Virol. Suppl.
|volume=12
|issue=
|pages=119–28
|year=1996
|pmid=9015109
}}</ref> as the immune system provides some protection.<ref name="pmid8793926">{{cite journal
|author=Velázquez FR, Matson DO, Calva JJ, Guerrero L, Morrow AL, Carter-Campbell S, Glass RI, Estes MK, Pickering LK, Ruiz-Palacios GM
|title=Rotavirus infections in infants as protection against subsequent infections
|journal=N. Engl. J. Med.
|volume=335
|issue=14
|pages=1022–8
|year=1996
|pmid=8793926
|url=http://content.nejm.org/cgi/content/full/335/14/1022
|doi=10.1056/NEJM199610033351404
}}</ref> Consequently, symptomatic infection rates are highest in children under two years of age and decrease progressively towards 45 years of age.<ref name="pmid1649875">{{cite journal
|author=Bernstein DI, Sander DS, Smith VE, Schiff GM, Ward RL
|title=Protection from rotavirus reinfection: 2-year prospective study
|journal=J. Infect. Dis.
|volume=164
|issue=2
|pages=277–83
|year=1991
|pmid=1649875
}}</ref><ref name="pmid2549788">{{cite journal
|author=Koopman JS, Monto AS
|title=The Tecumseh Study. XV: Rotavirus infection and pathogenicity
|journal=Am. J. Epidemiol.
|volume=130
|issue=4
|pages=750–9
|year=1989
|pmid=2549788
}}</ref> Infection in newborn children, although common, is often associated with mild or asymptomatic disease;<ref name="pmid209058">{{cite journal
|author=Cameron DJ, Bishop RF, Veenstra AA, Barnes GL
|title=Noncultivable viruses and neonatal diarrhea: Fifteen-month survey in a newborn special care nursery
|journal=J. Clin. Microbiol.
|volume=8
|issue=1
|pages=93–8
|year=1978
|pmid=209058
|url=http://jcm.asm.org/cgi/reprint/8/1/93
|format=PDF
}}</ref><ref name="pmid3003889">{{cite journal
|author=Grillner L, Broberger U, Chrystie I, Ransjö U
|title=Rotavirus infections in newborns: an epidemiological and clinical study
|journal=Scand. J. Infect. Dis.
|volume=17
|issue=4
|pages=349–55
|year=1985
|pmid=3003889
}}</ref> the most severe symptoms tend to occur in children six months to two years of age, the elderly, and those with [[immunodeficiency|compromised or absent immune system functions]]. 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.<ref name="pmid3037675">{{cite journal
|author=Hrdy DB
|title=Epidemiology of rotaviral infection in adults
|journal=Rev. Infect. Dis.
|volume=9
|issue=3
|pages=461–9
|year=1987
|pmid=3037675
}}</ref> Symptomatic reinfections are often due to a different rotavirus A serotype.<ref name="pmid2849961">{{cite journal
|author=Linhares AC, Gabbay YB, Mascarenhas JD, Freitas RB, Flewett TH, Beards GM
|title=Epidemiology of rotavirus subgroups and serotypes in Belem, Brazil: a three-year study
|journal=Ann. Inst. Pasteur Virol.
|volume=139
|issue=1
|pages=89–99
|year=1988
|pmid=2849961
|doi=10.1016/S0769-2617(88)80009-1
}}</ref><ref name="pmid1647052">{{cite journal
|author=De Champs C, Laveran H, Peigue-Lafeuille H, ''et al''
|title=Sequential rotavirus infections: characterization of serotypes and electrophoretypes
|journal=Res. Virol.
|volume=142
|issue=1
|pages=39–45
|year=1991
|pmid=1647052
|doi=10.1016/0923-2516(91)90026-Y
}}</ref>
== Transmission ==
[[Image:Multiple rotavirus particles.jpg|right|thumb|Rotavirus A from the [[faeces]] of an infected child]]
Rotavirus is transmitted by the [[fecal-oral route|faecal-oral route]], via contact with contaminated hands, surfaces and objects,<ref name="pmid8393172">{{cite journal
|author=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=202–5
|year=1993
|pmid=8393172
}}</ref> and possibly by the respiratory route.<ref name="pmid11052397">{{cite journal
|author=Dennehy PH
|title=Transmission of rotavirus and other enteric pathogens in the home
|journal=Pediatr. Infect. Dis. J.
|volume=19
|issue=10 Suppl
|pages=S103–5
|year=2000
|pmid=11052397
|doi=10.1097/00006454-200010001-00003
}}</ref> The faeces of an infected person can contain more than 10 trillion infectious particles per gram;<ref name="pmid9015109">{{cite journal
|author=Bishop RF
|title=Natural history of human rotavirus infection
|journal=Arch. Virol. Suppl.
|volume=12
|issue=
|pages=119–28
|year=1996
|pmid=9015109
}}</ref> only 10–100 of these are required to transmit infection to another person.<ref name="pmid3028333">{{cite journal
|author=Graham DY, Dufour GR, Estes MK
|title=Minimal infective dose of rotavirus
|journal=Arch. Virol.
|volume=92
|issue=3–4
|pages=261–71
|year=1987
|pmid=3028333
|doi=10.1007/BF01317483
}}</ref>
Rotaviruses are stable in the environment and have been found in [[estuary]] samples at levels as high as 1–5 infectious particles per US gallon.<ref name="pmid6091548">{{cite journal |author=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=Appl. Environ. Microbiol. |volume=48 |issue=2 |pages=404–9 |year=1984 |pmid=6091548 |url=http://aem.asm.org/cgi/reprint/48/2/404 |format=PDF}}</ref> Sanitary measures adequate for eliminating [[bacteria]] and [[parasite]]s seem to be ineffective in control of rotavirus, as the incidence of rotavirus infection in countries with high and low health standards is similar.<ref name="pmid11052397">{{cite journal |author=Dennehy PH |title=Transmission of rotavirus and other enteric pathogens in the home |journal=Pediatr. Infect. Dis. J. |volume=19 |issue=10 Suppl |pages=S103–5 |year=2000 |pmid=11052397 |doi=10.1097/00006454-200010001-00003}}</ref>
==Disease mechanisms==
[[Image:Rotavirus infected gut.jpg|right|thumb|Electron micrograph of a rotavirus infected enterocyte (top) compared to an uninfected cell (bottom). The bar = approx. 500 nm]]
The diarrhoea is caused by multiple activities of the virus. [[Malabsorption]] occurs because of the destruction of gut cells called [[enterocyte]]s. The [[enterotoxin|toxic]] rotavirus protein [[NSP4 (rotavirus)|NSP4]] induces age- and [[calcium]] ion-dependent [[chloride]] secretion, disrupts [[Sodium-glucose transport proteins|SGLT1]] [[Membrane transport protein|transporter]]-mediated reabsorption of water, apparently reduces activity of [[Brush border|brush-border membrane]] [[disaccharidase]]s, and possibly activates the calcium ion-dependent [[secretion|secretory]] [[reflex]]es of the [[enteric nervous system]].<ref name="pmid15802952">{{cite journal
|author=Ball JM, Mitchell DM, Gibbons TF, Parr RD
|title=Rotavirus NSP4: a multifunctional viral enterotoxin
|journal=Viral Immunol.
|volume=18
|issue=1
|pages=27–40
|year=2005
|pmid=15802952
|doi=10.1089/vim.2005.18.27
}}</ref><ref name="pmid17376232">{{cite journal
|author=Lorrot M, Vasseur M
|title=How do the rotavirus NSP4 and bacterial enterotoxins lead differently to diarrhea?
|journal=Virol. J.
|volume=4
|issue=
|pages=31
|year=2007
|pmid=17376232
|doi=10.1186/1743-422X-4-31
|url=http://www.virologyj.com/content/4//31
}}</ref> Healthy enterocytes secrete [[lactase]] into the small intestine; milk intolerance due to lactase deficiency is a particular symptom of rotavirus infection,<ref name="pmid9696817">{{cite journal
|author=Jourdan N, Brunet JP, Sapin C, ''et al''
|title=Rotavirus infection reduces sucrase-isomaltase expression in human intestinal epithelial cells by perturbing protein targeting and organization of microvillar cytoskeleton
|journal=J. Virol.
|volume=72
|issue=9
|pages=7228–36
|year=1998
|pmid=9696817
|url=http://jvi.asm.org/cgi/content/full/72/9/7228
}}</ref><ref name="pmid217231">{{cite journal
|author=Davidson GP, Barnes GL
|title=Structural and functional abnormalities of the small intestine in infants and young children with rotavirus enteritis
|journal=Acta. Paediatr. Scand.
|volume=68
|issue=2
|pages=181–6
|year=1979
|pmid=217231
|doi=10.1111/j.1651-2227.1979.tb04986.x
}}</ref> which can persist for weeks.<ref name="pmid12811680">{{cite journal
|author=Ouwehand A, Vesterlund S
|title=Health aspects of probiotics
|journal=IDrugs
|volume=6
|issue=6
|pages=573–80
|year=2003
|pmid=12811680
}}</ref> 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.<ref name="pmid6436397">{{cite journal
|author=Arya SC
|title=Rotaviral infection and intestinal lactase level
|journal=J. Infect. Dis.
|volume=150
|issue=5
|pages=791
|year=1984
|pmid=6436397
}}</ref>
==Diagnosis and detection==
Diagnosis of infection with rotavirus normally follows diagnosis of [[gastroenteritis]] as the cause of severe diarrhoea. Most children admitted to hospital with gastroenteritis are tested for {{nowrap|rotavirus A.}}<ref name="pmid17901797">{{cite journal |author=Patel MM, Tate JE, Selvarangan R, ''et al'' |title=Routine laboratory testing data for surveillance of rotavirus hospitalizations to evaluate the impact of vaccination |journal=Pediatr. Infect. Dis. J. |volume=26 |issue=10 |pages=914–9 |year=2007 |pmid=17901797 |doi=10.1097/INF.0b013e31812e52fd |doi_brokendate=2008-06-26}}</ref><ref name="pmid16650331">{{cite journal |author=The Pediatric ROTavirus European CommitTee (PROTECT) |title=The paediatric burden of rotavirus disease in Europe |journal=Epidemiol. Infect. |volume=134 |issue=5 |pages=908–16 |year=2006 |pmid=16650331 |doi=10.1017/S0950268806006091}}</ref>
Specific [[diagnosis]] of infection with {{nowrap|rotavirus A}} is made by identification of the virus in the patient's [[Human feces|stool]] by [[enzyme immunoassay]]. There are several licensed test kits on the market which are sensitive, specific and detect all serotypes of {{ nowrap|rotavirus A}}.<ref name="pmid8345165">{{cite journal
|author=Smith TF, Wold AD, Espy MJ, Marshall WF
|title=New developments in the diagnosis of viral diseases
|journal=Infect. Dis. Clin. North Am.
|volume=7
|issue=2
|pages=183–201
|year=1993
|pmid=8345165
}}</ref><ref name="pmid6321549"/> Other methods, [[electron microscopy]] and [[polyacrylamide gel electrophoresis]], are used in research laboratories.<ref name="pmid3132369">{{cite journal |author=Beards GM |title=Laboratory diagnosis of viral gastroenteritis |journal=Eur. J. Clin. Microbiol. Infect. Dis. |volume=7 |issue=1 |pages=11–3 |year=1988 |pmid=3132369 |doi=10.1007/BF01962164}}</ref> Reverse transcription-polymerase chain reaction ([[RT-PCR]]) can detect and identify all species and serotypes of human rotavirus.<ref name="pmid15027000">{{cite journal |author=Fischer TK, Gentsch JR |title=Rotavirus typing methods and algorithms |journal=Rev. Med. Virol. |volume=14 |issue=2 |pages=71–82 |year=2004 |pmid=15027000 |doi=10.1002/rmv.411}}</ref>
==Treatment and prognosis==
Treatment of acute rotavirus infection is nonspecific and involves management of symptoms and, most importantly, maintenance of [[Rehydration|hydration]].<ref name="pmid18026034">{{cite journal
|author=Diggle L
|title=Rotavirus diarrhoea and future prospects for prevention
|journal=Br. J. Nurs.
|volume=16
|issue=16
|pages=970–4
|year=2007
|pmid=18026034
}}</ref> If untreated, children can die from the resulting severe dehydration.<ref name="pmid12608880">{{cite journal
|author=Alam NH, Ashraf H
|title=Treatment of infectious diarrhea in children
|journal=Paediatr. Drugs
|volume=5
|issue=3
|pages=151–65
|year=2003
|pmid=12608880
}}</ref> Depending on the severity of [[diarrhea|diarrhoea]], treatment consists of [[Oral rehydration therapy|oral rehydration]] with plain water, water plus salts, or water plus salts and sugar.<ref name="pmid8855579">{{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}}</ref> Some infections are serious enough to warrant hospitalisation where fluids are given by [[intravenous]] drip or [[nasogastric tube]], and the child's [[electrolyte]]s and [[blood sugar]] are monitored.<ref name="pmid17901797">{{cite journal |author=Patel MM, Tate JE, Selvarangan R, Daskalaki I, Jackson MA, Curns AT, Coffin S, Watson B, Hodinka R, Glass RI, Parashar UD |title=Routine laboratory testing data for surveillance of rotavirus hospitalizations to evaluate the impact of vaccination |journal=Pediatr. Infect. Dis. J. |volume=26 |issue=10 |pages=914–9 |year=2007 |pmid=17901797 |doi=10.1097/INF.0b013e31812e52fd |doi_brokendate=2008-06-26}}</ref>
Rotavirus infections rarely cause other complications and for a well managed child the prognosis is excellent.<ref name="pmid1649479">{{cite journal
|author=Haffejee IE
|title=The pathophysiology, clinical features and management of rotavirus diarrhoea
|journal=Q. J. Med.
|volume=79
|issue=288
|pages=289–99
|year=1991
|pmid=1649479
|url=http://qjmed.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=1649479
}}</ref><ref name="pmid17678424">{{cite journal |author=Ramig RF |title=Systemic rotavirus infection |journal=Expert review of anti-infective therapy |volume=5 |issue=4 |pages=591–612 |year=2007 |pmid=17678424 |doi=10.1586/14787210.5.4.591}}</ref> There are rare reports of complications involving the [[central nervous system]] (CNS) where rotavirus was detected in the fluid of the CNS in cases of [[encephalitis]] and [[meningitis]],<ref name="pmid17852929">{{cite journal |author=Goto T, Kimura H, Numazaki K, ''et al'' |title=A case of meningoencephalitis associated with G1P[8] rotavirus infection in a Japanese child |journal=Scand. J. Infect. Dis. |volume=39 |issue=11 |pages=1067–70 |year=2007 |pmid=17852929 |doi=10.1080/00365540701466249}}</ref><ref name="pmid12797316">{{cite journal |author=Kehle J, Metzger-Boddien C, Tewald F, Wald M, Schüürmann J, Enders G |title=First case of confirmed rotavirus meningoencephalitis in Germany |journal=Pediatr. Infect. Dis. J. |volume=22 |issue=5 |pages=468–70 |year=2003 |pmid=12797316 |doi=10.1097/00006454-200305000-00020}}</ref><ref name="pmid10957919">{{cite journal |author=Pager C, Steele D, Gwamanda P, Driessen M |title=A neonatal death associated with rotavirus infection—detection of rotavirus dsRNA in the cerebrospinal fluid |journal=S. Afr. Med. J. |volume=90 |issue=4 |pages=364–5 |year=2000 |pmid=10957919}}</ref> and recent studies have confirmed that rotavirus infection is not always confined to the gut, but can cause [[viremia]].<ref name="pmid15687881">{{cite journal
|author=Widdowson MA, Bresee JS, Gentsch JR, Glass RI
|title=Rotavirus disease and its prevention
|journal=Curr. Opin. Gastroenterol.
|volume=21
|issue=1
|pages=26–31
|year=2005
|pmid=15687881
|url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=0267-1379&volume=21&issue=1&spage=26
}}</ref>
==Epidemiology==
[[Image:Rotavirus seasonal distribution.png|left|thumb|The seasonal variation of rotavirus A infections in a region of England: rates of infection peak during the winter months.]]
Rotavirus A, which accounts for more than 90% of rotavirus gastroenteritis in humans,<ref name="pmid16418157">{{cite journal
|author=Leung AK, Kellner JD, Davies HD
|title=Rotavirus gastroenteritis
|journal=Adv. Ther.
|volume=22
|issue=5
|pages=476–87
|year=2005
|pmid=16418157
|doi=10.1007/BF02849868
}}</ref> is [[Endemic (epidemiology)|endemic]] worldwide. Each year rotavirus causes millions of cases of diarrhoea in developing countries, almost 2 million resulting in hospitalisation<ref name="pmid17919334"/> and an estimated 611,000 resulting in death.<ref name="pmid16494759">{{cite journal
|author=Parashar UD, Gibson CJ, Bresse JS, Glass RI
|title=Rotavirus and severe childhood diarrhea
|journal=Emerging Infect. Dis.
|volume=12
|issue=2
|pages=304–6
|year=2006
|pmid=16494759
}}</ref> In the United States alone, over 2.7 million cases of rotavirus gastroenteritis occur annually, 60,000 children are hospitalised and around 37 die from the results of the infection.<ref name="pmid17357047">{{cite journal |author=Fischer TK, Viboud C, Parashar U, ''et al'' |title=Hospitalizations and deaths from diarrhea and rotavirus among children <5 years of age in the United States, 1993–2003 |journal=J. Infect. Dis. |volume=195 |issue=8 |pages=1117–25 |year=2007 |pmid=17357047 |doi=10.1086/512863}}</ref> The major role of rotavirus in causing diarrhoea is not widely recognised within the public health community, particularly in developing countries.<ref name="pmid17919334">{{cite journal
|author=Simpson E, Wittet S, Bonilla J, Gamazina K, Cooley L, Winkler JL
|title=Use of formative research in developing a knowledge translation approach to rotavirus vaccine introduction in developing countries
|journal=BMC Public Health
|volume=7
|issue=
|pages=281
|year=2007
|pmid=17919334
|doi=10.1186/1471-2458-7-281
|url=http://www.biomedcentral.com/1471-2458/7/281
}}</ref> Almost every child has been infected with rotavirus by age five.<ref name="pmid16494759"/> It is the leading single cause of severe diarrhoea among infants and children, being responsible for about 20% of cases, and accounts for 50% of the cases requiring hospitalisation.<ref name="pmid17919334">{{cite journal
|author=Simpson E, Wittet S, Bonilla J, Gamazina K, Cooley L, Winkler JL
|title=Use of formative research in developing a knowledge translation approach to Rotavirus vaccine introduction in developing countries
|journal=BMC Public Health
|volume=7
|issue=1
|pages=281
|year=2007
|pmid=17919334
|doi=10.1186/1471-2458-7-281
|url=http://www.biomedcentral.com/1471-2458/7/281
}}</ref> Boys are twice as likely to be admitted to hospital as girls.<ref name="pmid16397429">{{cite journal |author=Rheingans RD, Heylen J, Giaquinto C |title=Economics of rotavirus gastroenteritis and vaccination in Europe: what makes sense? |journal=Pediatr. Infect. Dis. J. |volume=25 |issue=1 Suppl |pages=S48–55 |year=2006 |pmid=16397429 |doi=10.1097/01.inf.0000197566.47750.3d}}</ref><ref name="pmid8752285">{{cite journal |author=Ryan MJ, Ramsay M, Brown D, Gay NJ, Farrington CP, Wall PG |title=Hospital admissions attributable to rotavirus infection in England and Wales |journal=J. Infect. Dis. |volume=174 Suppl 1 |pages=S12–8 |year=1996 |pmid=8752285}}</ref>
{| class = "prettytable" style = "float:right; font-size:85%; margin-left:15px; width:50%; text-align:center"
|+ Children dead before age 5 due to rotavirus A
! Country !! Rate or range !! Published !! Source
|-
! [[Vietnam]]
| 1 in 61 to 1 in 113 || 2006 ||<ref name="pmid16395100">{{cite journal
|author=Anh DD, Thiem VD, Fischer TK, Canh DG, Minh TT, Tho le H, Van Man N, Luan le T, Kilgore P, von Seidlein L, Glass RI
|title=The burden of rotavirus diarrhea in Khanh Hoa Province, Vietnam: baseline assessment for a rotavirus vaccine trial
|journal=Pediatr. Infect. Dis. J.
|volume=25
|issue=1
|pages=37–40
|year=2006
|pmid=16395100
}}</ref>
|-
! [[Bangladesh]]
| 1 in 390 to 1 in 660 ||2007||<ref name="pmid17984808">{{cite journal
|author=Tanaka G, Faruque AS, Luby SP, Malek MA, Glass RI, Parashar UD
|title=Deaths from rotavirus disease in Bangladeshi children: estimates from hospital-based surveillance
|journal=Pediatr. Infect. Dis. J.
|volume=26
|issue=11
|pages=1014–8
|year=2007
|pmid=17984808
|doi=10.1097/INF.0b013e318125721c
|doi_brokendate=2008-06-26
}}</ref>
|-
! [[Venezuela]]
| 1 in 1800 ||2007||<ref name="pmid17468648">{{cite journal
|author=Pérez-Schael I, Salinas B, González R, Salas H, Ludert JE, Escalona M, Alcalá A, Rosas MA, Materán M
|title=Rotavirus mortality confirmed by etiologic identification in Venezuelan children with diarrhea
|journal=Pediatr. Infect. Dis. J.
|volume=26
|issue=5
|pages=393–7
|year=2007
|pmid=17468648
|doi=10.1097/01.inf.0000260252.48129.86
}}</ref>
|-
! [[European Union]]
| 1 in 20433 ||2006||<ref name="pmid16397431">{{cite journal
|author=Soriano-Gabarró M, Mrukowicz J, Vesikari T, Verstraeten T
|title=Burden of rotavirus disease in European Union countries
|journal=Pediatr. Infect. Dis. J.
|volume=25
|issue=1 Suppl
|pages=S7–S11
|year=2006
|pmid=16397431
|doi=10.1097/01.inf.0000197622.98559.01
}}</ref>
|-
! [[United States]]
|1 in 21675||2007||<ref name="pmid17357047"/>
|}
In temperate areas, rotavirus infections occur primarily in the winter, but in the tropics they occur throughout the year;<ref name="pmid1694734">{{cite journal
|author=Cook SM, Glass RI, LeBaron CW, Ho MS
|title=Global seasonality of rotavirus infections
|journal=Bull. World Health Organ.
|volume=68
|issue=2
|pages=171–7
|year=1990
|pmid=1694734
}}</ref> the difference is partly explained by seasonal changes in temperature and humidity.<ref name="pmid6307226">{{cite journal
|author=Moe K, Harper GJ
|title=The effect of relative humidity and temperature on the survival of bovine rotavirus in aerosol
|journal=Arch. Virol.
|volume=76
|issue=3
|pages=211–6
|year=1983
|pmid=6307226
|doi=10.1007/BF01311105
}}</ref><ref name="pmid6287970">{{cite journal
|author=Moe K, Shirley JA
|title=The effects of relative humidity and temperature on the survival of human rotavirus in faeces
|journal=Arch. Virol.
|volume=72
|issue=3
|pages=179–86
|year=1982
|pmid=6287970
|doi=10.1007/BF01348963
}}</ref> The number attributable to food contamination is unknown.<ref name="pmid10088906">{{cite journal |author=Koopmans M, Brown D |title=Seasonality and diversity of Group A rotaviruses in Europe |journal=Acta paediatrica (Oslo, Norway : 1992). Supplement |volume=88 |issue=426 |pages=14–9 |year=1999 |pmid=10088906 |doi=10.1111/j.1651-2227.1999.tb14320.x}}</ref>
Outbreaks of rotavirus A diarrhoea are common among hospitalised infants, young children attending day care centres, and elderly people in nursing homes. An outbreak caused by contaminated municipal water occurred in Colorado in 1981.<ref name="pmid6320684">{{cite journal |author=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=263–5 |year=1984 |pmid=6320684 |url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=6320684}}</ref>
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.<ref name="pmid17229854">{{cite journal |author=Bucardo F, Karlsson B, Nordgren J, ''et al'' |title=Mutated G4P<nowiki>[8]</nowiki> rotavirus associated with a nationwide outbreak of gastroenteritis in Nicaragua in 2005 |journal=J. Clin. Microbiol. |volume=45 |issue=3 |pages=990–7 |year=2007 |pmid=17229854 |doi=10.1128/JCM.01992-06 |url=http://jcm.asm.org/cgi/content/full/45/3/990}}</ref> A similar large outbreak occurred in Brazil in 1977.<ref name="pmid6263087">{{cite journal |author=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=Am. J. Epidemiol. |volume=113 |issue=6 |pages=703–10 |year=1981 |pmid=6263087}}</ref>
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.<ref name="pmid6144874">{{cite journal |author=Hung T, Chen GM, Wang CG, ''et al'' |title=Waterborne outbreak of rotavirus diarrhea in adults in China caused by a novel rotavirus |journal=Lancet |volume=1 |issue=8387 |pages=1139–42 |year=1984 |pmid=6144874}}</ref><ref name="pmid2555422">{{cite journal |author=Fang ZY, Ye Q, Ho MS, ''et al'' |title=Investigation of an outbreak of adult diarrhea rotavirus in China |journal=J. Infect. Dis. |volume=160 |issue=6 |pages=948–53 |year=1989 |pmid=2555422}}</ref> Rotavirus B infections also occurred in India in 1998; the causative strain was named CAL. Unlike ADRV, the CAL strain is endemic.<ref name="pmid15310177">{{cite journal |author=Kelkar SD, Zade JK |title=Group B rotaviruses similar to strain CAL-1, have been circulating in Western India since 1993 |journal=Epidemiol. Infect. |volume=132 |issue=4 |pages=745–9 |year=2004 |pmid=15310177 |doi=10.1017/S0950268804002171}}</ref><ref name="pmid14635024">{{cite journal |author=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=J. Med. Virol. |volume=72 |issue=1 |pages=149–55 |year=2004 |pmid=14635024 |doi=10.1002/jmv.10546}}</ref> To date, epidemics caused by rotavirus B have been confined to [[mainland China]], but surveys indicate a lack of immunity to this species in the United States.<ref name="pmid2479654">{{cite journal |author=Penaranda ME, Ho MS, Fang ZY, ''et al'' |title=Seroepidemiology of adult diarrhea rotavirus in China, 1977 to 1987 |journal=J. Clin. Microbiol. |volume=27 |issue=10 |pages=2180–3 |year=1989 |pmid=2479654 |url=http://jcm.asm.org/cgi/reprint/27/10/2180 |format=PDF}}</ref>
Rotavirus C has been associated with rare and sporadic cases of diarrhoea in children in many countries, and outbreaks have occurred in Japan and England.<ref name="pmid17596825">{{cite journal |author=Kuzuya M, Fujii R, Hamano M, Nishijima M, Ogura H |title=Detection and molecular characterization of human group C rotaviruses in Okayama Prefecture, Japan, between 1986 and 2005 |journal=J. Med. Virol. |volume=79 |issue=8 |pages=1219–28 |year=2007 |pmid=17596825 |doi=10.1002/jmv.20910}}</ref><ref name="pmid2570978">{{cite journal |author=Brown DW, Campbell L, Tomkins DS, Hambling MH |title=School outbreak of gastroenteritis due to atypical rotavirus |journal=Lancet |volume=2 |issue=8665 |pages=737–8 |year=1989 |pmid=2570978 |doi=10.1016/S0140-6736(89)90794-0}}</ref>
== Prevention ==
{{main|Rotavirus Vaccine Program}}
In 2003, the [[World Health Organization]] and the United States [[Centers for Disease Control and Prevention]] established the [[Rotavirus Vaccine Program]] to reduce child [[morbidity]] and [[Mortality rate|mortality]] from diarrhoeal disease by making a vaccine against rotavirus available for use in developing countries.<ref name="pmid16860702">{{cite journal |author=Glass RI, Parashar UD, Bresee JS, ''et al'' |title=Rotavirus vaccines: current prospects and future challenges |journal=Lancet |volume=368 |issue=9532 |pages=323–32 |year=2006 |pmid=16860702 |doi=10.1016/S0140-6736(06)68815-6}}</ref>
In 2006, two vaccines against Rotavirus A infection were shown to be safe and effective in children: Rotarix by [[GlaxoSmithKline]]<ref name="pmid17280473">{{cite journal |author=O'Ryan M |title=Rotarix (RIX4414): an oral human rotavirus vaccine |journal=Expert review of vaccines |volume=6 |issue=1 |pages=11–9 |year=2007 |pmid=17280473 |doi=10.1586/14760584.6.1.11}}</ref> and RotaTeq by [[Merck & Co., Inc.|Merck]].<ref name="pmid17055370">{{cite journal |author=Matson DO |title=The pentavalent rotavirus vaccine, RotaTeq |journal=Seminars in paediatric infectious diseases |volume=17 |issue=4 |pages=195–9 |year=2006 |pmid=17055370 |doi=10.1053/j.spid.2006.08.005}}</ref> Both are taken orally and contain disabled live virus. Rotavirus vaccines are available in Australia, <ref>{{cite press release|url=http://www.gsk.com.au/media-centre_detail.aspx?view=54|title=Rotarix vaccine launched in Australia |publisher=GlaxoSmithKline|date=2006-05-14|accessdate=2008-06-14}}</ref> Europe,<ref>{{cite press release|url=http://www.gsk.com/ControllerServlet?appId=4&pageId=402&newsid=748|title=Rotarix : First vaccine against rotavirus available in Europe |publisher=GlaxoSmithKline|date=2006-02-27|accessdate=2008-02-07}}</ref> Canada,<ref>{{cite press release|url= http://www.merckfrosst.ca/assets/en/pdf/press/product_info/rotateq/press_releases/Release_NATIONAL_CNW.pdf|title=RotaTeq Is Approved In Canada|publisher=Merck Frosst Canada|date=2006-08-23|accessdate=2008-02-29}}</ref> Brazil,<ref>{{cite press release|url= http://portalweb05.saude.gov.br/portal/aplicacoes/noticias/noticias_detalhe.cfm?co_seq_noticia=24336|title=Rotavírus: vacina começa a ser aplicada no SUS|publisher=Ministério da Saúde|date=2006-06-03|accessdate=2008-03-10}}</ref> Israel, Panama and the United States.<ref>{{cite journal |author=Tom-Revzon C |title=Rotavirus live, oral, pentavalent vaccine |journal=Clin. Ther. |volume=29 |issue=12 |pages=2724–37 |year=2007 |pmid=18201590 |doi=10.1016/j.clinthera.2007.12.018}}</ref>
==Infections of animals==
Rotaviruses infect and cause diarrhoea in young animals. They have been shown to infect mammals (for example, apes,<ref name="pmid79844">{{cite journal |author=Ashley CR, Caul EO, Clarke SK, Corner BD, Dunn S |title=Rotavirus infections of apes |journal=Lancet |volume=2 |issue=8087 |pages=477 |year=1978 |pmid=79844 |doi=10.1016/S0140-6736(78)91485-X}}</ref> cattle,<ref name="pmid15861888">{{cite journal |author=Wani SA, Bhat MA, Ishaq SM, Ashrafi MA |title=Determination of bovine rotavirus G genotypes in Kashmir, India |journal=Rev. - Off. Int. Epizoot. |volume=23 |issue=3 |pages=931–6 |year=2004 |pmid=15861888}}</ref> pigs,<ref name="pmid9890034">{{cite journal |author=Saif LJ |title=Enteric viral infections of pigs and strategies for induction of mucosal immunity |journal=Advances in veterinary medicine |volume=41 |pages=429–46 |year=1999 |pmid=9890034}}</ref> sheep,<ref name="pmid2224836">{{cite journal |author=Holland RE |title=Some infectious causes of diarrhea in young farm animals |journal=Clin. Microbiol. Rev. |volume=3 |issue=4 |pages=345–75 |year=1990 |pmid=2224836|url=http://cmr.asm.org/cgi/reprint/3/4/345 |format=PDF}}</ref> rats,<ref name="pmid17957154">{{cite journal |author=Pérez-Cano FJ, Castell M, Castellote C, Franch A |title=Characterization of Clinical and Immune Response in a Rotavirus Diarrhea Model in Suckling Lewis Rats |journal=Pediatr Res |year=2007 |pmid=17957154 |doi=10.1203/PDR.0b013e318159a273 |doi_brokendate=2008-06-26}}</ref> cats and dogs,<ref name="pmid11512628">{{cite journal |author=Enriquez C, Nwachuku N, Gerba CP |title=Direct exposure to animal enteric pathogens |journal=Reviews on environmental health |volume=16 |issue=2 |pages=117–31 |year=2001 |pmid=11512628}}</ref> mice,<ref name="pmid9192019">{{cite journal |author=Feng N, Franco MA, Greenberg HB |title=Murine model of rotavirus infection |journal=Adv. Exp. Med. Biol. |volume=412 |pages=233–40 |year=1997 |pmid=9192019}}</ref> horses,<ref name="pmid1647407">{{cite journal |author=Hardy ME, Woode GN, Xu ZC, ''et al'' |title=Analysis of serotypes and electropherotypes of equine rotaviruses isolated in the United States |journal=J. Clin. Microbiol. |volume=29 |issue=5 |pages=889–93 |year=1991 |month=May |pmid=1647407 |pmc=269902 |doi= |url=http://jcm.asm.org/cgi/pmidlookup?view=long&pmid=1647407}}</ref> rabbits)<ref name="pmid2838507">{{cite journal |author=Thouless ME, DiGiacomo RF, Deeb BJ, Howard H |title=Pathogenicity of rotavirus in rabbits |journal=J. Clin. Microbiol. |volume=26 |issue=5 |pages=943–7 |year=1988 |pmid=2838507 |url=http://jcm.asm.org/cgi/reprint/26/5/943 |format=PDF}}</ref> and birds (chickens and turkeys).<ref name="pmid9706084">{{cite journal |author=Guy JS |title=Virus infections of the gastrointestinal tract of poultry |journal=Poult. Sci. |volume=77 |issue=8 |pages=1166–75 |year=1998 |pmid=9706084|url=http://ps.fass.org/cgi/reprint/77/8/1166 | format=PDF}}</ref> 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 [[Reassortment|reassortants]] with human strains.<ref name="pmid17416132">{{cite journal |author=Müller H, Johne R |title=Rotaviruses: diversity and zoonotic potential—a brief review |journal=Berl. Munch. Tierarztl. Wochenschr. |volume=120 |issue=3–4 |pages=108–12 |year=2007 |pmid=17416132}}</ref><ref name="pmid15066329">{{cite journal |author=Cook N, Bridger J, Kendall K, Gomara MI, El-Attar L, Gray J |title=The zoonotic potential of rotavirus |journal=J. Infect. |volume=48 |issue=4 |pages=289–302 |year=2004 |pmid=15066329 |doi=10.1016/j.jinf.2004.01.018}}</ref> Rotavirus are a pathogen of livestock and cause economic loss to farmers because of costs of treatment associated with high morbidity and mortality rates.<ref name="pmid2224836">{{cite journal |author=Holland RE |title=Some infectious causes of diarrhea in young farm animals |journal=Clin. Microbiol. Rev. |volume=3 |issue=4 |pages=345–75 |year=1990 |pmid=2224836}}</ref>
==Virology==
===Types of rotavirus===
There are seven species of rotavirus, referred to as A, B, C, D, E, F and G. Humans are primarily infected by species A, B and C, most commonly by species A. All seven species cause disease in other animals.<ref name="pmid2833405">{{cite journal |author=Beards GM, Brown DW |title=The antigenic diversity of rotaviruses: Significance to epidemiology and vaccine strategies |journal=Eur. J. Epidemiol. |volume=4 |issue=1 |pages=1–11 |year=1988 |pmid=2833405 |doi=10.1007/BF00152685}}</ref>
Within rotavirus A there are different strains, called [[serovar|serotype]]s.<ref name="pmid15484186">{{cite journal |author=Santos N, Hoshino Y |title=Global distribution of rotavirus serotypes/genotypes and its implication for the development and implementation of an effective rotavirus vaccine |journal=Rev. Med. Virol. |volume=15 |issue=1 |pages=29–56 |year=2005 |pmid=15484186 |doi=10.1002/rmv.448}}</ref> As with [[Influenza|influenza virus]], a dual classification system is used, which is based on two structural proteins on the surface of the virion. The [[glycoprotein]] VP7 defines G-types and the [[protease]]-sensitive protein VP4 defines P-types (see below for details on these proteins). The P-type is indicated by a number for the P-serotype and by a number in square brackets for the corresponding P-[[genotype]]. G-serotypes are similarly numbered but the G-genotype number is the same as the G-serotype. For example, the rotavirus strain Wa is defined as P1A<nowiki>[8]</nowiki>G1.<ref name="pmid11444024">{{cite journal |author=Desselberger U, Iturriza-Gómara M, Gray JJ |title=Rotavirus epidemiology and surveillance |journal=Novartis Found. Symp. |volume=238 |pages=125–47; discussion 147–52 |year=2001 |pmid=11444024}}</ref> Because the two genes that determine G-types and P-types can be passed on separately to offspring, various combinations occur in any one strain.<ref name="pmid16397427">{{cite journal
|author=Desselberger U, Wolleswinkel-van den Bosch J, Mrukowicz J, Rodrigo C, Giaquinto C, Vesikari T
|title=Rotavirus types in Europe and their significance for vaccination
|journal=Pediatr. Infect. Dis. J.
|volume=25
|issue=1 Suppl.
|pages=S30–41
|year=2006
|pmid=16397427
|url=http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?an=00006454-200601001-00005
|doi=10.1097/01.inf.0000197707.70835.f3
}}</ref>
===Structure===
The [[genome]] of rotavirus consists of 11 unique double helix molecules of [[RNA]] which are 18,555 [[nucleoside]] base-pairs 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 and 11, which each code for two.<ref name="pmid3010552">{{cite journal |author=Chan WK, Penaranda ME, Crawford SE, Estes MK |title=Two glycoproteins are produced from the rotavirus neutralization gene |journal=Virology |volume=151 |issue=2 |pages=243–52 |year=1986 |pmid=3010552 |doi=10.1016/0042-6822(86)90046-2}}</ref> The RNA is surrounded by a three-layered [[truncated icosahedron|icosahedral]] protein [[capsid]]. Viral particles are up to 76.5 nm in diameter<ref name="pmid16913048">{{cite journal |author=Pesavento JB, Crawford SE, Estes MK, Prasad BV |title=Rotavirus proteins: structure and assembly |journal=Curr. Top. Microbiol. Immunol. |volume=309 |pages=189–219 |year=2006 |pmid=16913048}}</ref><ref name="pmid8050286">{{cite journal |author=Prasad BV, Chiu W |title=Structure of rotavirus |journal=Curr. Top. Microbiol. Immunol. |volume=185 |pages=9–29 |year=1994 |pmid=8050286}}</ref> and are not enveloped.
===Proteins===
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 (rotavirus)|NSP1]], [[NSP2 (rotavirus)|NSP2]], [[NSP3 (rotavirus)|NSP3]], [[NSP4 (rotavirus)|NSP4]], [[NSP5 (rotavirus)|NSP5]] and [[NSP6 (rotavirus)|NSP6]].
[[Image:Rotavirus Structure.png|left|thumb|A simplified diagram of the location of rotavirus structural proteins]]
At least six of the twelve proteins [[coding region|encoded]] by the rotavirus genome bind [[RNA]].<ref name="pmid7595370">{{cite journal
|author=Patton JT
|title=Structure and function of the rotavirus RNA-binding proteins
|journal=J. Gen. Virol.
|volume=76 (Pt 11)
|pages=2633–44
|year=1995
|pmid=7595370
|url=http://vir.sgmjournals.org/cgi/reprint/76/11/2633
|format=PDF
|doi=10.1099/0022-1317-76-11-2633
}}</ref> The role of these proteins play 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 journal
|author=Patton JT
|title=Rotavirus RNA replication and gene expression
|journal=Novartis Found. Symp.
|volume=238
|pages=64–77; discussion 77–81
|year=2001
|pmid=11444036
}}</ref>
====Structural proteins====
VP1 is located in the core of the virus particle and is an [[RNA polymerase]] [[enzyme]].<ref name="pmid17657346">{{cite journal |author=Vásquez-del Carpió R, Morales JL, Barro M, Ricardo A, Spencer E |title=Bioinformatic prediction of polymerase elements in the rotavirus VP1 protein |journal=Biol. Res. |volume=39 |issue=4 |pages=649–59 |year=2006 |pmid=17657346 |doi=/S0716-97602006000500008 |url=http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602006000500008&tlng=en&lng=en&nrm=iso |doi_brokendate=2008-06-26}}</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.
[[Image:Rotavirus with gold- labelled monoclonal antibody.jpg|left|thumb|
Electron micrograph of gold nanoparticles binding to rotavirus. The small dark circular objects are gold nanoparticles coated with a [[monoclonal antibody]] specific for rotavirus protein VP6.]]
VP2 forms the core layer of the virion and binds the RNA genome.<ref name="pmid17182692">{{cite journal |author=Arnoldi F, Campagna M, Eichwald C, Desselberger U, Burrone OR |title=Interaction of rotavirus polymerase VP1 with nonstructural protein NSP5 is stronger than that with NSP2 |journal=J. Virol. |volume=81 |issue=5 |pages=2128–37 |year=2007 |pmid=17182692 |doi=10.1128/JVI.01494-06 |url=http://jvi.asm.org/cgi/content/full/81/5/2128}}</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>{{cite journal |author=Fresco LD, Buratowski S |title=Active site of the mRNA-capping enzyme guanylyltransferase from Saccharomyces cerevisiae: similarity to the nucleotidyl attachment motif of DNA and RNA ligases |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=91 |issue=14 |pages=6624–8 |year=1994 |pmid=8022828 |url=http://www.pnas.org/cgi/reprint/91/14/6624 |format=PDF |doi=10.1073/pnas.91.14.6624}}</ref> The cap stabilises viral mRNA by protecting it from [[nucleic acid]] degrading enzymes called [[nucleases]].
VP4 is on the surface of the virion that protrudes as a spike.<ref name="pmid16571811">{{cite journal |author=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=J. Virol. |volume=80 |issue=8 |pages=3947–56 |year=2006 |pmid=16571811 |doi=10.1128/JVI.80.8.3947-3956.2006 |url=http://jvi.asm.org/cgi/content/full/80/8/3947}}</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 |author=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=Arch. Med. Res. |volume=33 |issue=4 |pages=356–61 |year=2002 |pmid=12234525 |doi=10.1016/S0188-4409(02)00374-0}}</ref> VP4 has to be modified by a [[protease]] enzyme (found in the gut) into VP5* and VP8* before the virus is infectious.<ref name="pmid8384014">{{cite journal |author=Konno T, Suzuki H, Kitaoka S, Sato T, Fukuhara N, Yoshie O, Fukudome K, Numazaki Y |title=Proteolytic enhancement of human rotavirus infectivity |journal=Clin. Infect. Dis. |volume=16 Suppl 2 |pages=S92–7 |year=1993 |pmid=8384014}}</ref> It determines how [[virulent]] the virus is and it determines the P-type of the virus.<ref name="pmid12167342">{{cite journal |author=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}}</ref>
VP6 forms the bulk of the capsid. It is highly [[antigen]]ic and can be used to identify rotavirus species.<ref name="pmid9015109">{{cite journal |author=Bishop RF |title=Natural history of human rotavirus infection |journal=Arch. Virol. Suppl. |volume=12 |pages=119–28 |year=1996 |pmid=9015109}}</ref> This protein is used in laboratory tests for rotavirus A infections.<ref name="pmid6321549">{{cite journal |author=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=J. Clin. Microbiol. |volume=19 |issue=2 |pages=248–54 |year=1984 |pmid=6321549 |url=http://jcm.asm.org/cgi/reprint/19/2/248 |format=PDF}}</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">{{cite journal |author=Pesavento JB, Crawford SE, Estes MK, Prasad BV |title=Rotavirus proteins: structure and assembly |journal=Curr. Top. Microbiol. Immunol. |volume=309 |pages=189–219 |year=2006 |pmid=16913048}}</ref>
====Nonstructural viral proteins====
NSP1, the product of gene 5, is a [[nonstructural protein|nonstructural]] RNA-binding protein.<ref>{{cite journal |author=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=372–8 |year=1993 |pmid=8395125 |doi=10.1006/viro.1993.1492}}</ref>
NSP2 is an [[RNA-binding protein]] that accumulates in cytoplasmic inclusions ([[viroplasm]]s) and is required for genome replication.<ref>{{cite journal |author=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}}</ref><ref name="pmid15010217">{{cite journal |author=Taraporewala ZF, Patton JT |title=Nonstructural proteins involved in genome packaging and replication of rotaviruses and other members of the Reoviridae |journal=Virus Res. |volume=101 |issue=1 |pages=57–66 |year=2004 |pmid=15010217 |doi=10.1016/j.virusres.2003.12.006}}</ref>
NSP3 is bound to viral mRNAs in infected cells and it is responsible for the shutdown of cellular protein synthesis.<ref>{{cite journal |author=Poncet D, Aponte C, [[Jean Cohen|Cohen J]] |title=Rotavirus protein NSP3 (NS34) is bound to the 3' end consensus sequence of viral mRNAs in infected cells
|journal=J. Virol. |volume=67 |issue=6 |pages=3159–65 |year=1993 |pmid=8388495 |url=http://jvi.asm.org/cgi/reprint/67/6/3159 |format=PDF}}</ref>
NSP4 is a viral [[enterotoxin]] to induce diarrhoea and was the first viral enterotoxin discovered.<ref name='pmid9108087'>{{cite journal |author=Dong Y, Zeng CQ, Ball JM, Estes MK, Morris AP |title=The rotavirus enterotoxin NSP4 mobilizes intracellular calcium in human intestinal cells by stimulating phospholipase C-mediated inositol 1,4,5-trisphosphate production |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=94 |issue=8 |pages=3960–5 |year=1997 |pmid=9108087 |url=http://www.pnas.org/cgi/content/full/94/8/3960 |doi=10.1073/pnas.94.8.3960}}</ref>
NSP5 is encoded by genome segment 11 of rotavirus A and in virus-infected cells NSP5 accumulates in the viroplasm.<ref>{{cite journal |author=Afrikanova I, Miozzo MC, Giambiagi S, Burrone O |title=Phosphorylation generates different forms of rotavirus NSP5 |journal=J. Gen. Virol. |volume=77 ( Pt 9) |pages=2059–65 |year=1996 |pmid=8811003 |url=http://vir.sgmjournals.org/cgi/reprint/77/9/2059 |doi=10.1099/0022-1317-77-9-2059}}</ref>
NSP6 is a nucleic acid binding protein,<ref>{{cite journal |author=Rainsford EW, McCrae MA |title=Characterization of the NSP6 protein product of rotavirus gene 11 |journal=Virus Res. |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 |author=Mohan KV, Atreya CD |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=321–9 |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 !! Molecular weight [[Atomic mass unit|kDa]] !! Location!!Function
|-
! 1
| 3302 || VP1 || 125 || At the vertices of the core ||RNA-dependent RNA polymerase
|-
! 2
| 2690 || VP2 ||102|| Forms inner shell of the core || Stimulates viral RNA replicase
|-
! 3
| 2591 || VP3 ||88|| At the vertices of the core || Guanylyl transferase mRNA capping enzyme
|-
! 4
| 2362 || VP4 ||87|| Surface spike || Cell attachment, virulence
|-
!5
|1611||[[NSP1 (rotavirus)|NSP1]]||59||Nonstructural||Not essential to virus growth
|-
!6
|1356||VP6||45||Inner Capsid||Structural and species-specific antigen
|-
!7
|1104||[[NSP3 (rotavirus)|NSP3]]||37||Nonstructural||Enhances viral mRNA activity and shut-offs cellular protein synthesis
|-
!8
|1059||[[NSP2 (rotavirus)|NSP2]]||35||Nonstructural||NTPase involved in RNA packaging
|-
!9
|1062||VP7<sup>1</sup> VP7<sup>2</sup>||38 and 34||Surface||Structural and neutralisation antigen
|-
!10
|751||[[NSP4 (rotavirus)|NSP4]]||20||Nonstructural ||Enterotoxin
|-
!11
|667||[[NSP5 (rotavirus)|NSP5]] [[NSP6 (rotavirus)|NSP6]]||22||Nonstructural|| ssRNA and dsRNA binding modulator of [[NSP2 (rotavirus)|NSP2]]
|}
This table is based on the [[simian]] rotavirus strain SA11.<ref>Desselberger U. Rotavirus: basic facts. In ''Rotaviruses Methods and Protocols''. Ed. Gray, J. and Desselberger U. Humana Press, 2000, pp. 1–8. ISBN 0-89603-736-3</ref><ref>Patton JT. Rotavirus RNA replication and gene expression. In Novartis Foundation. ''Gastroenteritis Viruses'', Humana Press, 2001, pp. 64–81. ISBN 0-471-49663-4</ref> RNA-protein coding assignments differ in some strains.
===Replication===
[[Image:Rotavirus replication.png|thumb|right|300px|A simplified drawing of the rotavirus replication cycle]]
Rotavirus infects enterocytes of the [[Intestinal villus|villi]] of the [[small intestine]], leading to structural and functional changes of the [[epithelium]].<ref name="pmid8050281">{{cite journal
|author=Greenberg HB, Clark HF, Offit PA
|title=Rotavirus pathology and pathophysiology
|journal=Curr. Top. Microbiol. Immunol.
|volume=185
|pages=255–83
|year=1994
|pmid=8050281
}}</ref> The triple [[protein]] coats make them resistant to the acidic [[pH]] of the stomach and the [[digestive enzyme]]s in the [[gut]].
The virus enter 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)|trimer]]s into single protein subunits, leaving the VP2 and VP6 protein coats around the viral dsRNA, forming a double-layered particle (DLP).
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 called [[RNA interference]] that are triggered by the presence of double-stranded RNA.
During the infection, rotavirus produces 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. 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 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">{{cite journal |author=Jayaram H, Estes MK, Prasad BV |title=Emerging themes in rotavirus cell entry, genome organization, transcription and replication |journal=Virus Res. |volume=101 |issue=1 |pages=67–81 |year=2004 |pmid=15010218 |doi=10.1016/j.virusres.2003.12.007}}</ref><ref name="pmid15579070">{{cite journal
|author=Patton JT, Vasquez-Del Carpio R, Spencer E
|title=Replication and transcription of the rotavirus genome
|journal=Curr. Pharm. Des.
|volume=10
|issue=30
|pages=3769–77
|year=2004
|pmid=15579070
|doi=10.2174/1381612043382620
}}</ref>
== See also ==
*[[Norovirus]]
*[[Bacterial gastroenteritis]]
==References==
{{reflist|2}}
==External links==
*[http://www.cdc.gov/ncidod/dvrd/revb/gastro/sad0406Glas7p.pdf New hope for defeating rotavirus. Scientific American. 2006 Apr;294(4)): 46–55.]
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