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==Virology==
==Virology==
===Transmission===
Norovirus is transmitted through person-to-person contact, food and water. Genotype GII.4 is mostly contact transmitted. Non-GII.4 genotypes such as GI.3, GI.6, GI.7, GII.3, GII.6 and GII.12 are mostly food-borne. Genogroup GI strains are more often transmitted through water. This is due to their higher stability in water compared to other strains of the virus.<ref name="pmid27211790">{{cite journal| author=de Graaf M, van Beek J, Koopmans MP| title=Human norovirus transmission and evolution in a changing world. | journal=Nat Rev Microbiol | year= 2016 | volume= 14 | issue= 7 | pages= 421-33 | pmid=27211790 | doi=10.1038/nrmicro.2016.48 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27211790  }} </ref><ref name="pmid19494060">{{cite journal| author=Lysén M, Thorhagen M, Brytting M, Hjertqvist M, Andersson Y, Hedlund KO| title=Genetic diversity among food-borne and waterborne norovirus strains causing outbreaks in Sweden. | journal=J Clin Microbiol | year= 2009 | volume= 47 | issue= 8 | pages= 2411-8 | pmid=19494060 | doi=10.1128/JCM.02168-08 | pmc=2725682 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19494060  }} </ref>
Norovirus is among top ranks of food born viruses, globally<ref name="pmid26633896">{{cite journal| author=Havelaar AH, Kirk MD, Torgerson PR, Gibb HJ, Hald T, Lake RJ | display-authors=etal| title=World Health Organization Global Estimates and Regional Comparisons of the Burden of Foodborne Disease in 2010. | journal=PLoS Med | year= 2015 | volume= 12 | issue= 12 | pages= e1001923 | pmid=26633896 | doi=10.1371/journal.pmed.1001923 | pmc=4668832 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26633896  }} </ref>. Transmission could occur in different stages of pre- and post-production of the food products. For instance, shellfish can be contaminated with fecal discharge in the water<ref name="pmid22440973">{{cite journal| author=Le Guyader FS, Atmar RL, Le Pendu J| title=Transmission of viruses through shellfish: when specific ligands come into play. | journal=Curr Opin Virol | year= 2012 | volume= 2 | issue= 1 | pages= 103-10 | pmid=22440973 | doi=10.1016/j.coviro.2011.10.029 | pmc=3839110 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22440973  }} </ref>, fresh and frozen berries could be contaminated through water contaminated by sewage or contact during harvesting. Viral outbreaks through food-borne transmission can lead to a mixture of the viral strain and increased risk of genetic recombination. Studies show that about 7% of the foodborne outbreaks have a common source<ref name="pmid21392431">{{cite journal| author=Verhoef L, Kouyos RD, Vennema H, Kroneman A, Siebenga J, van Pelt W | display-authors=etal| title=An integrated approach to identifying international foodborne norovirus outbreaks. | journal=Emerg Infect Dis | year= 2011 | volume= 17 | issue= 3 | pages= 412-8 | pmid=21392431 | doi=10.3201/eid1703.100979 | pmc=3166008 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21392431  }} </ref>. 
Norovirus also has a nosocomial transition, causing a major burden for health care services<ref name="pmid24981041">{{cite journal| author=Ahmed SM, Hall AJ, Robinson AE, Verhoef L, Premkumar P, Parashar UD | display-authors=etal| title=Global prevalence of norovirus in cases of gastroenteritis: a systematic review and meta-analysis. | journal=Lancet Infect Dis | year= 2014 | volume= 14 | issue= 8 | pages= 725-730 | pmid=24981041 | doi=10.1016/S1473-3099(14)70767-4 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24981041  }} </ref>. Immunocompromised patients may develop numerous norovirus variations due to the chronic infection. This intra-host viral variation may lead to the appearance of variants not similar to any of the ones of previous outbreaks, thus can escape the herd immunity.<ref name="pmid24648459">{{cite journal| author=Debbink K, Lindesmith LC, Ferris MT, Swanstrom J, Beltramello M, Corti D | display-authors=etal| title=Within-host evolution results in antigenically distinct GII.4 noroviruses. | journal=J Virol | year= 2014 | volume= 88 | issue= 13 | pages= 7244-55 | pmid=24648459 | doi=10.1128/JVI.00203-14 | pmc=4054459 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24648459  }} </ref><ref name="pmid27211790">{{cite journal| author=de Graaf M, van Beek J, Koopmans MP| title=Human norovirus transmission and evolution in a changing world. | journal=Nat Rev Microbiol | year= 2016 | volume= 14 | issue= 7 | pages= 421-33 | pmid=27211790 | doi=10.1038/nrmicro.2016.48 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27211790  }} </ref> 
To date, animal norovirus strains have not been reported to infect human population, but there has been evidence of intra-species transmission. Human norovirus has been detected in the stools of pigs, cattle and dogs.<ref name="pmid27211790">{{cite journal| author=de Graaf M, van Beek J, Koopmans MP| title=Human norovirus transmission and evolution in a changing world. | journal=Nat Rev Microbiol | year= 2016 | volume= 14 | issue= 7 | pages= 421-33 | pmid=27211790 | doi=10.1038/nrmicro.2016.48 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27211790  }} </ref>
===Structure===
===Structure===
*Norovirus genome structure and protein coding regions: the genome is positive-sense single stranded RNA encoding three open reading frames (ORF). ORF1 encodes the nonstructural proteins. ORF2 and ORF3 encode the major capsid (VP1) and minor structural protein (VP2), respectively.<ref name="pmid16168575">{{cite journal| author=Hardy ME| title=Norovirus protein structure and function. | journal=FEMS Microbiol Lett | year= 2005 | volume= 253 | issue= 1 | pages= 1-8 | pmid=16168575 | doi=10.1016/j.femsle.2005.08.031 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16168575  }} </ref>  
*Norovirus genome structure and protein coding regions: the genome is positive-sense single stranded RNA encoding three open reading frames (ORF). ORF1 encodes the nonstructural proteins. ORF2 and ORF3 encode the major capsid (VP1) and minor structural protein (VP2), respectively.<ref name="pmid16168575">{{cite journal| author=Hardy ME| title=Norovirus protein structure and function. | journal=FEMS Microbiol Lett | year= 2005 | volume= 253 | issue= 1 | pages= 1-8 | pmid=16168575 | doi=10.1016/j.femsle.2005.08.031 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16168575  }} </ref>  

Revision as of 18:52, 19 February 2021

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This page is about microbiologic aspects of the organism(s).  For clinical aspects of the disease, see Norovirus infection.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Norovirus is the cause of norovirus infection. Noroviruses (genus Norovirus) are a group of related, single-stranded RNA, nonenveloped viruses that cause acute gastroenteritis in humans. Noroviruses belong to the family Caliciviridae.

Causes

Common Causes

Less Common Causes

Norovirus

Norovirus was the first virus to present with gastroenteritis in human and was first identified from stool specimen[1]. The illness caused by this virus was primarily given the term “winter vomiting disease”, due to its prominent gastrointestinal manifestations[2]. An outbreak in 1968 at an elementary school in Norwalk lead to the identification of the virus. Norovirus is the leading cause of gastroenteritis among all age groups and is responsible for 64000 cases of diarrhea leading to hospitalization, 900,000 visits to the clinic among children of developed countries and 200,000 deaths among children below 5 in developing countries[3][4].

Virology

Structure

  • Norovirus genome structure and protein coding regions: the genome is positive-sense single stranded RNA encoding three open reading frames (ORF). ORF1 encodes the nonstructural proteins. ORF2 and ORF3 encode the major capsid (VP1) and minor structural protein (VP2), respectively.[5]
  • Structural proteins: Norovirus consists of 90 dimers of VP1 and one or two copies of the VP2.
    • VP1: This major structural protein encoded by ORF2, consists of 530–555 amino acids with calculated molecular weights of 58–60 kDa. The protein has two conserved domains and a central variable domain with antigenic characteristics defining the specificity of the strain. VP1 assembles into virus-like particles[6]. VP1 has two major domains; 1) the shell domain (S) and 2) the protruding domain (P). The S domain is on the N-terminal (225 amino acids), containing the elements for icosahedron formation[7]. The P domain is comprised of the remaining amino acids and has two subdomains of P1 and P2. The P domain contributes to the stability of the capsid and formation of protrusions on the virion. P2 has a hypervariable region which is thought to play a role in receptor binding, immune reaction and interactions of ABO blood group antigens associated with susceptibility to the viral infection.[8][5]
    • VP2: This minor structural protein encoded by ORF3, ranges from 208–268 amino acids with calculated molecular weights of 22–29 kDa. VP2 shows high sequence diversity among strains. The exact function of this protein in the virus is not yet known. It is suggested that VP2 might contribute in RNA genome packaging. VP2 is not necessary for viral particles assembly but it is necessary for the formation of an infection virus. [5]
  • Nonstructural proteins[5]
    • p48 (p37)
    • p22 (p20)
    • VPg
    • 3CLpro
    • RdRp

Life Cycle

Norovirus has a cytoplasmic replication. It attaches to the host receptors and enters the cell through endocytosis. Since, it is a positive sense virus, replication and transcription follows the corresponding models for positive stranded RNA viruses. Translation occurs by leaky scanning, and RNA termination-reinitiation.[9]

Genus Host Details Tissue Tropism Entry Details Release Details Replication Site Assembly Site Transmission
Norovirus Humans; mammals Intestinal epithelium Cell receptor endocytosis Lysis Cytoplasm Cytoplasm Oral-fecal

Gallery

References

  1. ↑ Kapikian AZ, Wyatt RG, Dolin R, Thornhill TS, Kalica AR, Chanock RM (1972). "Visualization by immune electron microscopy of a 27-nm particle associated with acute infectious nonbacterial gastroenteritis". J Virol. 10 (5): 1075–81. doi:10.1128/JVI.10.5.1075-1081.1972. PMC 356579. PMID 4117963.
  2. ↑ Lopman BA, Reacher M, Gallimore C, Adak GK, Gray JJ, Brown DW (2003). "A summertime peak of "winter vomiting disease": surveillance of noroviruses in England and Wales, 1995 to 2002". BMC Public Health. 3: 13. doi:10.1186/1471-2458-3-13. PMC 153520. PMID 12659651.
  3. ↑ Schmoldt A, Benthe HF, Haberland G (1975). "Digitoxin metabolism by rat liver microsomes". Biochem Pharmacol. 24 (17): 1639–41. PMID .3201/eid1408.071114. 10 .3201/eid1408.071114. Check |pmid= value (help).
  4. ↑ Robilotti E, Deresinski S, Pinsky BA (2015). "Norovirus". Clin Microbiol Rev. 28 (1): 134–64. doi:10.1128/CMR.00075-14. PMC 4284304. PMID 25567225.
  5. ↑ 5.0 5.1 5.2 5.3 Hardy ME (2005). "Norovirus protein structure and function". FEMS Microbiol Lett. 253 (1): 1–8. doi:10.1016/j.femsle.2005.08.031. PMID 16168575.
  6. ↑ Bertolotti-Ciarlet A, White LJ, Chen R, Prasad BV, Estes MK (2002). "Structural requirements for the assembly of Norwalk virus-like particles". J Virol. 76 (8): 4044–55. doi:10.1128/jvi.76.8.4044-4055.2002. PMC 136079. PMID 11907243.
  7. ↑ Prasad BV, Hardy ME, Dokland T, Bella J, Rossmann MG, Estes MK (1999). "X-ray crystallographic structure of the Norwalk virus capsid". Science. 286 (5438): 287–90. doi:10.1126/science.286.5438.287. PMID 10514371.
  8. ↑ Tan M, Huang P, Meller J, Zhong W, Farkas T, Jiang X (2003). "Mutations within the P2 domain of norovirus capsid affect binding to human histo-blood group antigens: evidence for a binding pocket". J Virol. 77 (23): 12562–71. doi:10.1128/jvi.77.23.12562-12571.2003. PMC 262557. PMID 14610179.
  9. ↑ Invalid <ref> tag; no text was provided for refs named ViralZone
  10. ↑ 10.0 10.1 10.2 10.3 10.4 10.5 10.6 "Public Health Image Library (PHIL)".


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