Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Murine norovirus, a recently discovered and highly prevalent viral agent of mice

Lab Animal volume 37, pages 314–320 (2008)Cite this article

Abstract

Murine norovirus (MNV), a recently discovered viral agent of laboratory mice, is closely related to human norovirus, a contagious pathogen known to cause gastroenteritis. The prototype strain of MNV (MNV-1) was first isolated and characterized in 2003 as a sporadic, lethal pathogen in certain strains of immunocompromised knockout mice. Serological surveillance data from mouse colonies throughout the US and Canada have since shown that MNV is highly prevalent. Because MNV is unique among norovirus strains in its ability to replicate in cell culture, it serves as the most accessible model to elucidate the mechanisms of infection and replication of human norovirus. The author discusses the genetic diversity of MNV, its prevalence, pathology and potential research implications, as well as techniques for detection and eradication of this virus.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Schematic diagram showing the organization of the MNV genome and putative cleavage products of the virus ORF1 polyprotein.

Similar content being viewed by others

References

  1. Karst, S.M., Wobus, C.E., Lay, M., Davidson, J. & Virgin, H.W. 4th. STAT1-dependent innate immunity to a Norwalk-like virus. Science 299, 1575–1578 (2003).

    Article  CAS  PubMed  Google Scholar 

  2. Yee, E.L. et al. Widespread outbreak of norovirus gastroenteritis among evacuees of Hurricane Katrina residing in a large “megashelter” in Houston, Texas: lessons learned for prevention. Clin. Infect. Dis. 44, 1032–1039 (2007).

    Article  PubMed  Google Scholar 

  3. National Institutes of Allergy and Infectious Diseases. Category A, B & C Priority Pathogens. [online] (2007).

  4. Centers for Disease Control. Agents, Diseases, and Other Threats. [online] (2007).

  5. Liu, B.L. et al. Molecular characterization of a bovine enteric calicivirus: relationship to the Norwalk-like viruses. J. Virol. 73, 819–825 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Wang, Q.H. et al. Porcine noroviruses related to human noroviruses. Emerg. Infect. Dis. 11, 1874–1881 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Wesoly, J., Szweykowska-Kulinska, Z. & Bluyssen, H.A. STAT activation and differential complex formation dictate selectivity of interferon responses. Acta Biochim. Pol. 54, 27–38 (2007).

    CAS  PubMed  Google Scholar 

  8. Wobus, C.E. et al. Replication of Norovirus in cell culture reveals a tropism for dendritic cells and macrophages. PLoS Biol. 2, e432 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Green, K.Y. et al. Taxonomy of the caliciviruses. J. Infect. Dis. 181 Suppl 2, S322–S330 (2000).

    Article  PubMed  Google Scholar 

  10. Blakeney, S.J., Cahill, A. & Reilly, P.A. Processing of Norwalk virus nonstructural proteins by a 3C-like cysteine proteinase. Virology 308, 216–224 (2003).

    Article  CAS  PubMed  Google Scholar 

  11. Liu, B., Clarke, I.N. & Lambden, P.R. Polyprotein processing in Southampton virus: identification of 3C-like protease cleavage sites by in vitro mutagenesis. J. Virol. 70, 2605–2610 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Liu, B.L., Viljoen, G.J., Clarke, I.N. & Lambden, P.R. Identification of further proteolytic cleavage sites in the Southampton calicivirus polyprotein by expression of the viral protease in E. coli. J. Gen. Virol. 80, 291–296 (1999).

    Article  CAS  PubMed  Google Scholar 

  13. Sosnovtsev, S.V. et al. Cleavage map and proteolytic processing of the murine norovirus nonstructural polyprotein in infected cells. J. Virol. 80, 7816–7831 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Jiang, X., Espul, C., Zhong, W.M., Cuello, H. & Matson, D.O. Characterization of a novel human calicivirus that may be a naturally occurring recombinant. Arch. Virol. 144, 2377–2387 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Prasad, B.V. et al. X-ray crystallographic structure of the Norwalk virus capsid. Science 286, 287–290 (1999).

    Article  CAS  PubMed  Google Scholar 

  16. Hale, A.D. et al. Identification of an epitope common to genogroup 1 “norwalk-like viruses”. J. Clin. Microbiol. 38, 1656–1660 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Hardy, M.E. et al. Antigenic mapping of the recombinant Norwalk virus capsid protein using monoclonal antibodies. Virology 217, 252–261 (1996).

    Article  CAS  PubMed  Google Scholar 

  18. Lochridge, V.P. Jutila, K.L., Graff, J.W. & Hardy, M.E. Epitopes in the P2 domain of norovirus VP1 recognized by monoclonal antibodies that block cell interactions. J. Gen. Virol. 86, 2799–2806 (2005).

    Article  CAS  PubMed  Google Scholar 

  19. Tan, M. et al. Mutations within the P2 domain of norovirus capsid affect binding to human histo-blood group antigens: evidence for a binding pocket. J. Virol. 77, 12562–12571 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hsu, C.C., Riley, L.K., Wills, H.M. & Livingston, R.S. Persistent infection with and serologic cross-reactivity of three novel murine noroviruses. Comp. Med. 56, 247–251 (2006).

    CAS  PubMed  Google Scholar 

  21. Thackray, L.B. et al. Murine noroviruses comprising a single genogroup and serotype exhibit biological diversity despite limited sequence divergence. J. Virol. 81, 10460–10473 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Hsu, C.C., Wobus, C.E., Steffen, E.K., Riley, L.K. & Livingston, R.S. Development of a microsphere-based serologic multiplexed fluorescent immunoassay and a reverse transcriptase PCR assay to detect murine norovirus 1 infection in mice. Clin. Diagn. Lab. Immunol. 12, 1145–1151 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Livingston, R.S. & Riley, L.K. Diagnostic testing of mouse and rat colonies for infectious agents. Lab Anim. (NY) 32, 44–51 (2003).

    Article  Google Scholar 

  24. Zheng, D.P. et al. Norovirus classification and proposed strain nomenclature. Virology 346, 312–323 (2006).

    Article  CAS  PubMed  Google Scholar 

  25. Katayama, K. et al. Phylogenetic analysis of the complete genome of 18 Norwalk-like viruses. Virology 299, 225–239 (2002).

    Article  CAS  PubMed  Google Scholar 

  26. Mumphrey, S.M. et al. Murine norovirus 1 infection is associated with histopathological changes in immunocompetent hosts, but clinical disease is prevented by STAT1-dependent interferon responses. J. Virol. 81, 3251–3263 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ward, J.M. et al. Pathology of immunodeficient mice with naturally occurring murine norovirus infection. Toxicol. Pathol. 34, 708–715 (2006).

    Article  PubMed  Google Scholar 

  28. Perdue, K.A. et al. Naturally occurring murine norovirus infection in a large research institution. J. Am. Assoc. Lab. Anim. Sci. 46, 39–45 (2007).

    CAS  PubMed  Google Scholar 

  29. Chase, K. et al. Murine Norovirus, an Intercurrent Variable in a Mouse Model of Bacterial-Induced Inflammatory Bowel Disease. 58th American Association for Laboratory Animal Science National Meeting. Charlotte, NC, 14–18 October 2007.

  30. Burton-MacLeod, J.A. et al. Evaluation and comparison of two commercial enzyme-linked immunosorbent assay kits for detection of antigenically diverse human noroviruses in stool samples. J. Clin. Microbiol. 42, 2587–2595 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Muller, B., Klemm, U., Mas Marques, A. & Schreier, E. Genetic diversity and recombination of murine noroviruses in immunocompromised mice. Arch. Virol. 152, 1709–1719 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Bertolotti-Ciarlet, A., Crawford, S.E., Hutson, A.M. & Estes, M.K. The 3′ end of Norwalk virus mRNA contains determinants that regulate the expression and stability of the viral capsid protein VP1: a novel function for the VP2 protein. J. Virol. 77, 11603–11615 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Clarke, I.N. & Lambden, P.R. Organization and expression of calicivirus genes. J. Infect. Dis. 181 Suppl 2, S309–S316 (2000).

    Article  CAS  PubMed  Google Scholar 

  34. Gutierrez-Escolano, A.L., Brito, Z.U., del Angel, R.M. & Jiang, X. Interaction of cellular proteins with the 5′ end of Norwalk virus genomic RNA. J. Virol. 74, 8558–8562 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Gutierrez-Escolano, A.L., Vazquez-Ochoa, M., Escobar-Herrera, J. & Hernandez-Acosta, J. La, PTB, and PAB proteins bind to the 3(') untranslated region of Norwalk virus genomic RNA. Biochem. Biophys. Res. Commun. 311, 759–766 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Pletneva, M.A., Sosnovtsev, S.V. & Green, K.Y. The genome of hawaii virus and its relationship with other members of the caliciviridae. Virus Genes 23, 5–16 (2001).

    Article  CAS  PubMed  Google Scholar 

  37. Cannon, J.L. et al. Surrogates for the study of norovirus stability and inactivation in the environment: aA comparison of murine norovirus and feline calicivirus. J. Food Prot. 69, 2761–2765 (2006).

    Article  PubMed  Google Scholar 

  38. Duizer, E. et al. Inactivation of caliciviruses. Appl. Environ. Microbiol. 70, 4538–4543 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. De Roda Husman, A.M. et al. Calicivirus inactivation by nonionizing (253.7-nanometer-wavelength [UV]) and ionizing (gamma) radiation. Appl. Environ. Microbiol. 70, 5089–5093 (2004).

    Article  PubMed  PubMed Central  Google Scholar 

  40. Thurston-Enriquez, J.A., Haas, C.N., Jacangelo, J., Riley, K. & Gerba, C.P. Inactivation of feline calicivirus and adenovirus type 40 by UV radiation. Appl. Environ. Microbiol. 69, 577–582 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kingsley, D.H., Holliman, D.R., Calci, K.R. Chen, H. & Flick, G.J. Inactivation of a norovirus by high-pressure processing. Appl. Environ. Microbiol. 73, 581–585 (2007).

    Article  CAS  PubMed  Google Scholar 

  42. Compton, S.R. Susceptibility of Neonatal Mice to Murine Norovirus Infection. 58th American Association for Laboratory Animal Science National Meeting. Charlotte, NC, 14–18 October 2007.

  43. Artwohl, J.E., Purcell, J.E., Chrusciel, K., Lang, M. & Fortman, J. Assessment of Cross-foster Rederivation in the Elimination of Mouse Norovirus and Helicobacter 58th American Association for Laboratory Animal Science National Meeting. Charlotte, NC, 14–18 October 2007.

Download references

Acknowledgements

I recognize Joseph Alexander for literature review and technical writing support and Bill Shek, Steve Jennings, Michelle Wunderlich, Laila Banu, Cheryl Perkins, Rajeev Dhawan, Joe Simmons, Larissa Thackray, Lisa White, Charlie Clifford and Walter Blank for research and review support.

Author information

Authors and Affiliations

  1. Molecular Diagnostics, Charles River, Wilmington, MA

    Kenneth S. Henderson

Authors
  1. Kenneth S. Henderson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kenneth S. Henderson.

Ethics declarations

Competing interests

The author declares no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Henderson, K. Murine norovirus, a recently discovered and highly prevalent viral agent of mice. Lab Anim 37, 314–320 (2008). https://doi.org/10.1038/laban0708-314

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/laban0708-314

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing