Norovirus

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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.

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

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.[5][6]

Norovirus is among top ranks of food born viruses, globally[7]. 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[8], 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[9].

Norovirus also has a nosocomial transition, causing a major burden for health care services[10]. 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.[11][5]

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.[5]

Classification

Norovirus could be classified into different genogroups and P (polymerase)-groups, then further into genotypes and P-types, based on diversity of amino acids of the complete VP1 gene and nucleotide diversity of the RNA-dependent RNA polymerase (RdRp) region of ORF1, respectively. The genus Norovirus consists of genogroups from GI to GX. Each of the genogroups, consist of 49 capsid genotypes (9 GI, 27 GII, 3 GIII, 2 GIV, 2 GV, 2 GVI and 1 genotype each for GVII, GVIII, GIX [formerly GII.15] and GX). There a few viruses classified into tentative new genogroups (GNA1 and GNA2) and genotypes (GII.NA1, GII.NA2 and GIV), of which only one sequence exists, awaiting additional sequences. Norovirus is classified into 60 P-types (14GI, 37 GII, 2 GIII, 1 GIV, 2 GV, 2 GVI, 1 GVII and 1 GX), based on nucleotide diversity of the RdRp region. Moreover, currently 2 tentative P-groups and 14 tentative P-types of Norovirus exists.[12]

Structure

Viruses in Norovirus are non-enveloped, with icosahedral geometries. Capsid diameters vary widely, from 23-40 nm in diameter. The larger capsids (38-40 nm) exhibit T=3 symmetry and are composed of 180 VP1 proteins. Small capsids (23 nm) show T=1 symmetry, and are composed of 60 VP1 proteins.[13] The virus particles demonstrate an amorphous surface structure when visualized using electron microscopy.[14]

Noroviruses contain a linear, non-segmented,[13] positive-sense RNA genome of approximately 7.5kbp, encoding a major structural protein (VP1) of about 58~60 kDa and a minor capsid protein (VP2).[15]

The most variable region of the viral capsid is the P2 domain, which contains antigen-presenting sites and carbohydrate-receptor binding regions.[16][17][18][19]

The estimated mutation rate (1.21Template:E to 1.41 Template:E substitutions per site per year) in this virus is high even compared with other RNA viruses.[20]

Genus Structure Symmetry Capsid Genomic Arrangement Genomic Segmentation
Norovirus Icosahedral T=1, T=3 Non-Enveloped Linear Monopartite

Life Cycle

Viral replication is cytoplasmic. Entry into the host cell is achieved by attachment to host receptors, which mediates endocytosis. Replication follows the positive stranded RNA virus replication model. Positive stranded RNA virus transcription is the method of transcription. Translation takes place by leaky scanning, and RNA termination-reinitiation. Human and mammals serve as the natural host. Transmission routes are fecal-oral and contamination.[13]

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 de Graaf M, van Beek J, Koopmans MP (2016). "Human norovirus transmission and evolution in a changing world". Nat Rev Microbiol. 14 (7): 421–33. doi:10.1038/nrmicro.2016.48. PMID 27211790.
  6. Lysén M, Thorhagen M, Brytting M, Hjertqvist M, Andersson Y, Hedlund KO (2009). "Genetic diversity among food-borne and waterborne norovirus strains causing outbreaks in Sweden". J Clin Microbiol. 47 (8): 2411–8. doi:10.1128/JCM.02168-08. PMC 2725682. PMID 19494060.
  7. Havelaar AH, Kirk MD, Torgerson PR, Gibb HJ, Hald T, Lake RJ; et al. (2015). "World Health Organization Global Estimates and Regional Comparisons of the Burden of Foodborne Disease in 2010". PLoS Med. 12 (12): e1001923. doi:10.1371/journal.pmed.1001923. PMC 4668832. PMID 26633896.
  8. Le Guyader FS, Atmar RL, Le Pendu J (2012). "Transmission of viruses through shellfish: when specific ligands come into play". Curr Opin Virol. 2 (1): 103–10. doi:10.1016/j.coviro.2011.10.029. PMC 3839110. PMID 22440973.
  9. Verhoef L, Kouyos RD, Vennema H, Kroneman A, Siebenga J, van Pelt W; et al. (2011). "An integrated approach to identifying international foodborne norovirus outbreaks". Emerg Infect Dis. 17 (3): 412–8. doi:10.3201/eid1703.100979. PMC 3166008. PMID 21392431.
  10. Ahmed SM, Hall AJ, Robinson AE, Verhoef L, Premkumar P, Parashar UD; et al. (2014). "Global prevalence of norovirus in cases of gastroenteritis: a systematic review and meta-analysis". Lancet Infect Dis. 14 (8): 725–730. doi:10.1016/S1473-3099(14)70767-4. PMID 24981041.
  11. Debbink K, Lindesmith LC, Ferris MT, Swanstrom J, Beltramello M, Corti D; et al. (2014). "Within-host evolution results in antigenically distinct GII.4 noroviruses". J Virol. 88 (13): 7244–55. doi:10.1128/JVI.00203-14. PMC 4054459. PMID 24648459.
  12. Chhabra P, de Graaf M, Parra GI, Chan MC, Green K, Martella V; et al. (2019). "Updated classification of norovirus genogroups and genotypes". J Gen Virol. 100 (10): 1393–1406. doi:10.1099/jgv.0.001318. PMC 7011714 Check |pmc= value (help). PMID 31483239.
  13. 13.0 13.1 13.2 "Viral Zone". ExPASy. Retrieved 15 June 2015.
  14. Prasad BV, Crawford S, Lawton JA, Pesavento J, Hardy M, Estes MK (2001). "Structural studies on gastroenteritis viruses". Novartis Found. Symp. Novartis Foundation Symposia. 238: 26–37, discussion 37–46. doi:10.1002/0470846534.ch3. ISBN 978-0-470-84653-7. PMID 11444031.
  15. Clarke IN, Lambden PR (2000). "Organization and expression of calicivirus genes". J. Infect. Dis. 181 Suppl 2: S309–16. doi:10.1086/315575. PMID 10804143.
  16. Tan M, Hegde RS, Jiang X (2004). "The P Domain of Norovirus Capsid Protein Forms Dimer and Binds to Histo-Blood Group Antigen Receptors". J. Virol. 78 (12): 6233–42. doi:10.1128/JVI.78.12.6233-6242.2004. PMC 416535. PMID 15163716.
  17. Tan M, Huang PW, Meller J, Zhong WM, Farkas T, Jiang X (2004). "Mutations within the P2 domain of norovirus capsid affect binding to human histo-blood group antigens: evidence for a binding pocket". J. Virol. 78 (6): 3201. doi:10.1128/JVI.78.6.3201.2004.
  18. Cao S, Lou Z, Tan M, Chen Y, Liu Y, Zhang Z, Zhang XC, Jiang X, Li X, Rao Z (2007). "Structural Basis for the Recognition of Blood Group Trisaccharides by Norovirus". J. Virol. 81 (11): 5949–57. doi:10.1128/JVI.00219-07. PMC 1900264. PMID 17392366.
  19. Lundborg M, Ali E, Widmalm G (2013). "An in silico virtual screening study for the design of norovirus inhibitors: fragment-based molecular docking and binding free energy calculations". Carbohydr Res. 378: 133–8. doi:10.1016/j.carres.2013.03.012. PMID 23582100.
  20. Victoria M, Miagostovich MP, Ferreira MS, Vieira CB, Fioretti JM, Leite JP, Colina R, Cristina J (2009). "Bayesian coalescent inference reveals high evolutionary rates and expansion of Norovirus populations". Infect Genet Evol. 9 (5): 927–932. doi:10.1016/j.meegid.2009.06.014. PMID 19559104.
  21. 21.0 21.1 21.2 21.3 21.4 21.5 21.6 "Public Health Image Library (PHIL)".


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