1887

Abstract

Human noroviruses (HuNoV) are a major cause of viral gastroenteritis worldwide, yet, due to the inability to propagate HuNoV in cell culture, murine norovirus (MNV) is typically used as a surrogate to study norovirus biology. MNV-3 represents an attractive strain to study norovirus infections because it establishes persistence in wild-type mice, yet causes symptoms resembling gastroenteritis in immune-compromised STAT1 mice. The lack of reverse-genetics approaches to recover genetically defined MNV-3 has limited further studies on the identification of viral sequences that contribute to persistence. Here we report the establishment of a combined DNA-based reverse-genetics and mouse-model system to study persistent MNV-3 infections in wild-type (C57BL/6) mice. Viral RNA and infectious virus were detected in faeces for at least 56 days after inoculation. Strikingly, the highest concentrations of viral RNA during persistence were detected in the caecum and colon, suggesting that viral persistence is maintained in these tissues. Possible adaptive changes arising during persistence appeared to accumulate in the minor capsid protein (VP2) and the viral polymerase (NS7), in contrast with adaptive mutations selected during cell-culture passages in RAW264.7 cells that appeared in the major capsid protein (VP1) and non-structural protein NS4. This system provides an attractive model that can be readily used to identify viral sequences that contribute to persistence in an immunocompetent host and to more acute infection in an immunocompromised host, providing new insights into the biology of norovirus infections.

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2012-07-01
2019-10-18
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References

  1. Arias A., Perales C., Escarmís C., Domingo E.. ( 2010;). Deletion mutants of VPg reveal new cytopathology determinants in a picornavirus. . PLoS ONE 5:, e10735. [CrossRef][PubMed]
    [Google Scholar]
  2. Bailey D., Thackray L. B., Goodfellow I. G.. ( 2008;). A single amino acid substitution in the murine norovirus capsid protein is sufficient for attenuation in vivo. . J Virol 82:, 7725–7728. [CrossRef][PubMed]
    [Google Scholar]
  3. Bailey D., Karakasiliotis I., Vashist S., Chung L. M., Rees J., McFadden N., Benson A., Yarovinsky F., Simmonds P., Goodfellow I.. ( 2010;). Functional analysis of RNA structures present at the 3′ extremity of the murine norovirus genome: the variable polypyrimidine tract plays a role in viral virulence. . J Virol 84:, 2859–2870. [CrossRef][PubMed]
    [Google Scholar]
  4. Barron E. L., Sosnovtsev S. V., Bok K., Prikhodko V., Sandoval-Jaime C., Rhodes C. R., Hasenkrug K., Carmody A. B., Ward J. M.. & other authors ( 2011;). Diversity of murine norovirus strains isolated from asymptomatic mice of different genetic backgrounds within a single U.S. research institute. . PLoS ONE 6:, e21435. [CrossRef][PubMed]
    [Google Scholar]
  5. Buchholz U. J., Finke S., Conzelmann K. K.. ( 1999;). Generation of bovine respiratory syncytial virus (BRSV) from cDNA: BRSV NS2 is not essential for virus replication in tissue culture, and the human RSV leader region acts as a functional BRSV genome promoter. . J Virol 73:, 251–259.[PubMed]
    [Google Scholar]
  6. Byrnes A. P., Griffin D. E.. ( 2000;). Large-plaque mutants of Sindbis virus show reduced binding to heparan sulfate, heightened viremia, and slower clearance from the circulation. . J Virol 74:, 644–651. [CrossRef][PubMed]
    [Google Scholar]
  7. Cadwell K., Patel K. K., Maloney N. S., Liu T. C., Ng A. C., Storer C. E., Head R. D., Xavier R., Stappenbeck T. S., Virgin H. W.. ( 2010;). Virus-plus-susceptibility gene interaction determines Crohn’s disease gene Atg16L1 phenotypes in intestine. . Cell 141:, 1135–1145. [CrossRef][PubMed]
    [Google Scholar]
  8. Capizzi T., Makari-Judson G., Steingart R., Mertens W. C.. ( 2011;). Chronic diarrhea associated with persistent norovirus excretion in patients with chronic lymphocytic leukemia: report of two cases. . BMC Infect Dis 11:, 131. [CrossRef][PubMed]
    [Google Scholar]
  9. CDC ( 2002;). Outbreak of acute gastroenteritis associated with Norwalk-like viruses among British military personnel – Afghanistan, May 2002. . MMWR Morb Mortal Wkly Rep 51:, 477–479.[PubMed]
    [Google Scholar]
  10. Chan M. C., Lee N., Ho W. S., Law C. O., Lau T. C., Tsui S. K., Sung J. J.. ( 2012;). Covariation of major and minor viral capsid proteins in norovirus genogroup II genotype 4 strains. . J Virol 86:, 1227–1232. [CrossRef][PubMed]
    [Google Scholar]
  11. Chaudhry Y., Nayak A., Bordeleau M. E., Tanaka J., Pelletier J., Belsham G. J., Roberts L. O., Goodfellow I. G.. ( 2006;). Caliciviruses differ in their functional requirements for eIF4F components. . J Biol Chem 281:, 25315–25325. [CrossRef][PubMed]
    [Google Scholar]
  12. Chaudhry Y., Skinner M. A., Goodfellow I. G.. ( 2007;). Recovery of genetically defined murine norovirus in tissue culture by using a fowlpox virus expressing T7 RNA polymerase. . J Gen Virol 88:, 2091–2100. [CrossRef][PubMed]
    [Google Scholar]
  13. Chen S. Y., Tsai C. N., Lai M. W., Chen C. Y., Lin K. L., Lin T. Y., Chiu C. H.. ( 2009;). Norovirus infection as a cause of diarrhea-associated benign infantile seizures. . Clin Infect Dis 48:, 849–855. [CrossRef][PubMed]
    [Google Scholar]
  14. Daughenbaugh K. F., Fraser C. S., Hershey J. W., Hardy M. E.. ( 2003;). The genome-linked protein VPg of the Norwalk virus binds eIF3, suggesting its role in translation initiation complex recruitment. . EMBO J 22:, 2852–2859. [CrossRef][PubMed]
    [Google Scholar]
  15. Daughenbaugh K. F., Wobus C. E., Hardy M. E.. ( 2006;). VPg of murine norovirus binds translation initiation factors in infected cells. . Virol J 3:, 33. [CrossRef][PubMed]
    [Google Scholar]
  16. Goodfellow I., Chaudhry Y., Gioldasi I., Gerondopoulos A., Natoni A., Labrie L., Laliberté J. F., Roberts L.. ( 2005;). Calicivirus translation initiation requires an interaction between VPg and eIF4E. . EMBO Rep 6:, 968–972. [CrossRef][PubMed]
    [Google Scholar]
  17. Harris J. R., Racaniello V. R.. ( 2005;). Amino acid changes in proteins 2B and 3A mediate rhinovirus type 39 growth in mouse cells. . J Virol 79:, 5363–5373. [CrossRef][PubMed]
    [Google Scholar]
  18. Harris J. P., Edmunds W. J., Pebody R., Brown D. W., Lopman B. A.. ( 2008;). Deaths from norovirus among the elderly, England and Wales. . Emerg Infect Dis 14:, 1546–1552. [CrossRef][PubMed]
    [Google Scholar]
  19. Hsu C. C., Riley L. K., Wills H. M., Livingston R. S.. ( 2006;). Persistent infection with and serologic cross-reactivity of three novel murine noroviruses. . Comp Med 56:, 247–251.[PubMed]
    [Google Scholar]
  20. Hsu C. C., Riley L. K., Livingston R. S.. ( 2007;). Molecular characterization of three novel murine noroviruses. . Virus Genes 34:, 147–155. [CrossRef][PubMed]
    [Google Scholar]
  21. Ito S., Takeshita S., Nezu A., Aihara Y., Usuku S., Noguchi Y., Yokota S.. ( 2006;). Norovirus-associated encephalopathy. . Pediatr Infect Dis J 25:, 651–652. [CrossRef][PubMed]
    [Google Scholar]
  22. Kahan S. M., Liu G., Reinhard M. K., Hsu C. C., Livingston R. S., Karst S. M.. ( 2011;). Comparative murine norovirus studies reveal a lack of correlation between intestinal virus titers and enteric pathology. . Virology 421:, 202–210. [CrossRef][PubMed]
    [Google Scholar]
  23. Karst S. M., Wobus C. E., Lay M., Davidson J., Virgin H. W. IV. ( 2003;). STAT1-dependent innate immunity to a Norwalk-like virus. . Science 299:, 1575–1578. [CrossRef][PubMed]
    [Google Scholar]
  24. Khan R. R., Lawson A. D., Minnich L. L., Martin K., Nasir A., Emmett M. K., Welch C. A., Udall J. N. Jr. ( 2009;). Gastrointestinal norovirus infection associated with exacerbation of inflammatory bowel disease. . J Pediatr Gastroenterol Nutr 48:, 328–333. [CrossRef][PubMed]
    [Google Scholar]
  25. Kitajima M., Oka T., Takagi H., Tohya Y., Katayama H., Takeda N., Katayama K.. ( 2010;). Development and application of a broadly reactive real-time reverse transcription-PCR assay for detection of murine noroviruses. . J Virol Methods 169:, 269–273. [CrossRef][PubMed]
    [Google Scholar]
  26. Koo H. L., Ajami N., Atmar R. L., DuPont H. L.. ( 2010;). Noroviruses: the leading cause of gastroenteritis worldwide. . Discov Med 10:, 61–70.[PubMed]
    [Google Scholar]
  27. Lee J. H., Alam I., Han K. R., Cho S., Shin S., Kang S., Yang J. M., Kim K. H.. ( 2011;). Crystal structures of murine norovirus-1 RNA-dependent RNA polymerase. . J Gen Virol 92:, 1607–1616. [CrossRef][PubMed]
    [Google Scholar]
  28. Lencioni K. C., Seamons A., Treuting P. M., Maggio-Price L., Brabb T.. ( 2008;). Murine norovirus: an intercurrent variable in a mouse model of bacteria-induced inflammatory bowel disease. . Comp Med 58:, 522–533.[PubMed]
    [Google Scholar]
  29. Lochridge V. P., Hardy M. E.. ( 2007;). A single-amino-acid substitution in the P2 domain of VP1 of murine norovirus is sufficient for escape from antibody neutralization. . J Virol 81:, 12316–12322. [CrossRef][PubMed]
    [Google Scholar]
  30. Lopman B. A., Reacher M. H., Vipond I. B., Hill D., Perry C., Halladay T., Brown D. W., Edmunds W. J., Sarangi J.. ( 2004;). Epidemiology and cost of nosocomial gastroenteritis, Avon, England, 2002–2003. . Emerg Infect Dis 10:, 1827–1834. [CrossRef][PubMed]
    [Google Scholar]
  31. Ludwig A., Adams O., Laws H. J., Schroten H., Tenenbaum T.. ( 2008;). Quantitative detection of norovirus excretion in pediatric patients with cancer and prolonged gastroenteritis and shedding of norovirus. . J Med Virol 80:, 1461–1467. [CrossRef][PubMed]
    [Google Scholar]
  32. McFadden N., Bailey D., Carrara G., Benson A., Chaudhry Y., Shortland A., Heeney J., Yarovinsky F., Simmonds P.. & other authors ( 2011;). Norovirus regulation of the innate immune response and apoptosis occurs via the product of the alternative open reading frame 4. . PLoS Pathog 7:, e1002413. [CrossRef][PubMed]
    [Google Scholar]
  33. Mead P. S., Slutsker L., Dietz V., McCaig L. F., Bresee J. S., Shapiro C., Griffin P. M., Tauxe R. V.. ( 1999;). Food-related illness and death in the United States. . Emerg Infect Dis 5:, 607–625. [CrossRef][PubMed]
    [Google Scholar]
  34. Monroe S. S.. ( 2011;). Control and prevention of viral gastroenteritis. . Emerg Infect Dis 17:, 1347–1348.[PubMed]
    [Google Scholar]
  35. Mumphrey S. M., Changotra H., Moore T. N., Heimann-Nichols E. R., Wobus C. E., Reilly M. J., Moghadamfalahi M., Shukla D., Karst S. M.. ( 2007;). 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. [CrossRef][PubMed]
    [Google Scholar]
  36. Núñez J. I., Baranowski E., Molina N., Ruiz-Jarabo C. M., Sánchez C., Domingo E., Sobrino F.. ( 2001;). A single amino acid substitution in nonstructural protein 3A can mediate adaptation of foot-and-mouth disease virus to the guinea pig. . J Virol 75:, 3977–3983. [CrossRef][PubMed]
    [Google Scholar]
  37. Patel M. M., Widdowson M. A., Glass R. I., Akazawa K., Vinjé J., Parashar U. D.. ( 2008;). Systematic literature review of role of noroviruses in sporadic gastroenteritis. . Emerg Infect Dis 14:, 1224–1231. [CrossRef][PubMed]
    [Google Scholar]
  38. Phillips G., Tam C. C., Rodrigues L. C., Lopman B.. ( 2010;). Prevalence and characteristics of asymptomatic norovirus infection in the community in England. . Epidemiol Infect 138:, 1454–1458. [CrossRef][PubMed]
    [Google Scholar]
  39. Sosnovtsev S. V., Belliot G., Chang K. O., Onwudiwe O., Green K. Y.. ( 2005;). Feline calicivirus VP2 is essential for the production of infectious virions. . J Virol 79:, 4012–4024. [CrossRef][PubMed]
    [Google Scholar]
  40. Sosnovtsev S. V., Belliot G., Chang K. O., Prikhodko V. G., Thackray L. B., Wobus C. E., Karst S. M., Virgin H. W., Green K. Y.. ( 2006;). Cleavage map and proteolytic processing of the murine norovirus nonstructural polyprotein in infected cells. . J Virol 80:, 7816–7831. [CrossRef][PubMed]
    [Google Scholar]
  41. Strong D. W., Thackray L. B., Smith T. J., Virgin H. W.. ( 2012;). Protruding domain of capsid protein is necessary and sufficient to determine murine norovirus replication and pathogenesis in vivo. . J Virol 86:, 2950–2958. [CrossRef][PubMed]
    [Google Scholar]
  42. Taube S., Rubin J. R., Katpally U., Smith T. J., Kendall A., Stuckey J. A., Wobus C. E.. ( 2010;). High-resolution X-ray structure and functional analysis of the murine norovirus 1 capsid protein protruding domain. . J Virol 84:, 5695–5705. [CrossRef][PubMed]
    [Google Scholar]
  43. Thackray L. B., Wobus C. E., Chachu K. A., Liu B., Alegre E. R., Henderson K. S., Kelley S. T., Virgin H. W. IV. ( 2007;). Murine noroviruses comprising a single genogroup exhibit biological diversity despite limited sequence divergence. . J Virol 81:, 10460–10473. [CrossRef][PubMed]
    [Google Scholar]
  44. van Asten L., Siebenga J., van den Wijngaard C., Verheij R., van Vliet H., Kretzschmar M., Boshuizen H., van Pelt W., Koopmans M.. ( 2011;). Unspecified gastroenteritis illness and deaths in the elderly associated with norovirus epidemics. . Epidemiology 22:, 336–343. [CrossRef][PubMed]
    [Google Scholar]
  45. Vernacchio L., Vezina R. M., Mitchell A. A., Lesko S. M., Plaut A. G., Acheson D. W.. ( 2006;). Characteristics of persistent diarrhea in a community-based cohort of young US children. . J Pediatr Gastroenterol Nutr 43:, 52–58. [CrossRef][PubMed]
    [Google Scholar]
  46. Walker S. C., Avis J. M., Conn G. L.. ( 2003;). General plasmids for producing RNA in vitro transcripts with homogeneous ends. . Nucleic Acids Res 31:, e82. [CrossRef][PubMed]
    [Google Scholar]
  47. Ward V. K., McCormick C. J., Clarke I. N., Salim O., Wobus C. E., Thackray L. B., Virgin H. W. IV, Lambden P. R.. ( 2007;). Recovery of infectious murine norovirus using pol II-driven expression of full-length cDNA. . Proc Natl Acad Sci U S A 104:, 11050–11055. [CrossRef][PubMed]
    [Google Scholar]
  48. Wobus C. E., Karst S. M., Thackray L. B., Chang K. O., Sosnovtsev S. V., Belliot G., Krug A., Mackenzie J. M., Green K. Y., Virgin H. W.. ( 2004;). Replication of norovirus in cell culture reveals a tropism for dendritic cells and macrophages. . PLoS Biol 2:, e432. [CrossRef][PubMed]
    [Google Scholar]
  49. Wobus C. E., Thackray L. B., Virgin H. W. IV. ( 2006;). Murine norovirus: a model system to study norovirus biology and pathogenesis. . J Virol 80:, 5104–5112. [CrossRef][PubMed]
    [Google Scholar]
  50. Yunus M. A., Chung L. M., Chaudhry Y., Bailey D., Goodfellow I.. ( 2010;). Development of an optimized RNA-based murine norovirus reverse genetics system. . J Virol Methods 169:, 112–118. [CrossRef][PubMed]
    [Google Scholar]
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