1887

Abstract

Subclinical infection of murine norovirus (MNV) was detected in a mixed breeding group of WT and mice with no outward evidence of morbidity or mortality. Investigations revealed the presence of an attenuated MNV variant that did not cause cytopathic effects in RAW264.7 cells or death in mice. Histopathological analysis of tissues from WT, heterozygous and mice revealed a surprising spectrum of lesions. An infectious molecular clone was derived directly from faeces (MNV-O7) and the sequence analysis confirmed it was a member of norovirus genogroup V. Experimental infection with MNV-O7 induced a subclinical infection with no weight loss in or WT mice, and recapitulated the clinical and pathological picture of the naturally infected colony. Unexpectedly, by day 54 post-infection, 50 % of mice had cleared MNV-O7. In contrast, all WT mice remained infected persistently. Most significantly, this was associated with liver lesions in all the subclinically infected WT mice. These data confirmed that long-term persistence in WT mice is established with specific variants of MNV and that despite a subclinical presentation, active foci of acute inflammation persist within the liver. The data also showed that STAT1-dependent responses are not required to protect mice from lethal infection with all strains of MNV.

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2014-02-01
2019-09-18
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References

  1. Agrawal S. , Febbraio M. , Podrez E. , Cathcart M. K. , Stark G. R. , Chisolm G. M. . ( 2007; ). Signal transducer and activator of transcription 1 is required for optimal foam cell formation and atherosclerotic lesion development. . Circulation 115:, 2939–2947. [CrossRef] [PubMed]
    [Google Scholar]
  2. Arias A. , Bailey D. , Chaudhry Y. , Goodfellow I. . ( 2012; ). Development of a reverse-genetics system for murine norovirus 3: long-term persistence occurs in the caecum and colon. . J Gen Virol 93:, 1432–1441. [CrossRef] [PubMed]
    [Google Scholar]
  3. 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]
  4. 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]
  5. Chachu K. A. , LoBue A. D. , Strong D. W. , Baric R. S. , Virgin H. W. . ( 2008a; ). Immune mechanisms responsible for vaccination against and clearance of mucosal and lymphatic norovirus infection. . PLoS Pathog 4:, e1000236. [CrossRef] [PubMed]
    [Google Scholar]
  6. Chachu K. A. , Strong D. W. , LoBue A. D. , Wobus C. E. , Baric R. S. , Virgin H. W. IV . ( 2008b; ). Antibody is critical for the clearance of murine norovirus infection. . J Virol 82:, 6610–6617. [CrossRef] [PubMed]
    [Google Scholar]
  7. 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]
  8. Coyne K. P. , Dawson S. , Radford A. D. , Cripps P. J. , Porter C. J. , McCracken C. M. , Gaskell R. M. . ( 2006; ). Long-term analysis of feline calicivirus prevalence and viral shedding patterns in naturally infected colonies of domestic cats. . Vet Microbiol 118:, 12–25. [CrossRef] [PubMed]
    [Google Scholar]
  9. Coyne K. P. , Gaskell R. M. , Dawson S. , Porter C. J. , Radford A. D. . ( 2007; ). Evolutionary mechanisms of persistence and diversification of a calicivirus within endemically infected natural host populations. . J Virol 81:, 1961–1971. [CrossRef] [PubMed]
    [Google Scholar]
  10. Forrester N. L. , Boag B. , Moss S. R. , Turner S. L. , Trout R. C. , White P. J. , Hudson P. J. , Gould E. A. . ( 2003; ). Long-term survival of New Zealand rabbit haemorrhagic disease virus RNA in wild rabbits, revealed by RT-PCR and phylogenetic analysis. . J Gen Virol 84:, 3079–3086. [CrossRef] [PubMed]
    [Google Scholar]
  11. Forrester N. L. , Moss S. R. , Turner S. L. , Schirrmeier H. , Gould E. A. . ( 2008; ). Recombination in rabbit haemorrhagic disease virus: possible impact on evolution and epidemiology. . Virology 376:, 390–396. [CrossRef] [PubMed]
    [Google Scholar]
  12. Gil M. P. , Bohn E. , O’Guin A. K. , Ramana C. V. , Levine B. , Stark G. R. , Virgin H. W. , Schreiber R. D. . ( 2001; ). Biologic consequences of Stat1-independent IFN signaling. . Proc Natl Acad Sci U S A 98:, 6680–6685. [CrossRef] [PubMed]
    [Google Scholar]
  13. Godinez I. , Raffatellu M. , Chu H. , Paixão T. A. , Haneda T. , Santos R. L. , Bevins C. L. , Tsolis R. M. , Bäumler A. J. . ( 2009; ). Interleukin-23 orchestrates mucosal responses to Salmonella enterica serotype Typhimurium in the intestine. . Infect Immun 77:, 387–398. [CrossRef] [PubMed]
    [Google Scholar]
  14. Gouy M. , Guindon S. , Gascuel O. . ( 2010; ). SeaView version 4: a multiplatform graphical user interface for sequence alignment and phylogenetic tree building. . Mol Biol Evol 27:, 221–224. [CrossRef] [PubMed]
    [Google Scholar]
  15. Guindon S. , Dufayard J. F. , Lefort V. , Anisimova M. , Hordijk W. , Gascuel O. . ( 2010; ). New algorithms and methods to estimate maximum-likelihood phylogenies: assessing the performance of PhyML 3.0. . Syst Biol 59:, 307–321. [CrossRef] [PubMed]
    [Google Scholar]
  16. 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]
  17. 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]
  18. Hübscher S. G. . ( 1998; ). Histological grading and staging in chronic hepatitis: clinical applications and problems. . J Hepatol 29:, 1015–1022. [CrossRef] [PubMed]
    [Google Scholar]
  19. Johnson R. P. . ( 1992; ). Antigenic change in feline calicivirus during persistent infection. . Can J Vet Res 56:, 326–330.[PubMed]
    [Google Scholar]
  20. 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]
  21. 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]
  22. Katpally U. , Wobus C. E. , Dryden K. , Virgin H. W. IV , Smith T. J. . ( 2008; ). Structure of antibody-neutralized murine norovirus and unexpected differences from viruslike particles. . J Virol 82:, 2079–2088. [CrossRef] [PubMed]
    [Google Scholar]
  23. 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]
  24. Malmgaard L. , Salazar-Mather T. P. , Lewis C. A. , Biron C. A. . ( 2002; ). Promotion of alpha/beta interferon induction during in vivo viral infection through alpha/beta interferon receptor/STAT1 system-dependent and -independent pathways. . J Virol 76:, 4520–4525. [CrossRef] [PubMed]
    [Google Scholar]
  25. Manuel C. A. , Hsu C. C. , Riley L. K. , Livingston R. S. . ( 2008; ). Soiled-bedding sentinel detection of murine norovirus 4. . J Am Assoc Lab Anim Sci 47:, 31–36.[PubMed]
    [Google Scholar]
  26. McFadden N. , Arias A. , Dry I. , Bailey D. , Witteveldt J. , Evans D. J. , Goodfellow I. , Simmonds P. . ( 2013; ). Influence of genome-scale RNA structure disruption on the replication of murine norovirus – similar replication kinetics in cell culture but attenuation of viral fitness in vivo . . Nucleic Acids Res 41:, 6316–6331. [CrossRef] [PubMed]
    [Google Scholar]
  27. Mohan R. R. , Mohan R. R. , Kim W. J. , Stark G. R. , Wilson S. E. . ( 2000; ). Defective keratocyte apoptosis in response to epithelial injury in Stat 1 null mice. . Exp Eye Res 70:, 485–491. [CrossRef] [PubMed]
    [Google Scholar]
  28. 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]
  29. Nice T. J. , Strong D. W. , McCune B. T. , Pohl C. S. , Virgin H. W. . ( 2013; ). A single-amino-acid change in murine norovirus NS1/2 is sufficient for colonic tropism and persistence. . J Virol 87:, 327–334. [CrossRef] [PubMed]
    [Google Scholar]
  30. Nicklas W. , Baneux P. , Boot R. , Decelle T. , Deeny A. A. , Fumanelli M. , Illgen-Wilcke B. . FELASA (Federation of European Laboratory Animal Science Associations Working Group on Health Monitoring of Rodent and Rabbit Colonies) ( 2002; ). Recommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units. . Lab Anim 36:, 20–42. [CrossRef] [PubMed]
    [Google Scholar]
  31. Oldstone M. B. . ( 2006; ). Viral persistence: parameters, mechanisms and future predictions. . Virology 344:, 111–118.[PubMed] [CrossRef]
    [Google Scholar]
  32. Radford A. D. , Turner P. C. , Bennett M. , McArdle F. , Dawson S. , Glenn M. A. , Williams R. A. , Gaskell R. M. . ( 1998; ). Quasispecies evolution of a hypervariable region of the feline calicivirus capsid gene in cell culture and in persistently infected cats. . J Gen Virol 79:, 1–10.[PubMed]
    [Google Scholar]
  33. Ramana C. V. , Gil M. P. , Schreiber R. D. , Stark G. R. . ( 2002; ). Stat1-dependent and -independent pathways in IFN-gamma-dependent signaling. . Trends Immunol 23:, 96–101. [CrossRef] [PubMed]
    [Google Scholar]
  34. Shresta S. , Sharar K. L. , Prigozhin D. M. , Snider H. M. , Beatty P. R. , Harris E. . ( 2005; ). Critical roles for both STAT1-dependent and STAT1-independent pathways in the control of primary dengue virus infection in mice. . J Immunol 175:, 3946–3954.[PubMed] [CrossRef]
    [Google Scholar]
  35. Siebenga J. J. , Beersma M. F. , Vennema H. , van Biezen P. , Hartwig N. J. , Koopmans M. . ( 2008; ). High prevalence of prolonged norovirus shedding and illness among hospitalized patients: a model for in vivo molecular evolution. . J Infect Dis 198:, 994–1001. [CrossRef] [PubMed]
    [Google Scholar]
  36. 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]
  37. 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]
  38. Theise N. D. . ( 2007; ). Liver biopsy assessment in chronic viral hepatitis: a personal, practical approach. . Mod Pathol 20: (Suppl 1), S3–S14. [CrossRef] [PubMed]
    [Google Scholar]
  39. Tomov V. T. , Osborne L. C. , Dolfi D. V. , Sonnenberg G. F. , Monticelli L. A. , Mansfield K. , Virgin H. W. , Artis D. , Wherry E. J. . ( 2013; ). Persistent enteric murine norovirus infection is associated with functionally suboptimal virus-specific CD8 T cell responses. . J Virol 87:, 7015–7031. [CrossRef] [PubMed]
    [Google Scholar]
  40. Ward J. M. , Wobus C. E. , Thackray L. B. , Erexson C. R. , Faucette L. J. , Belliot G. , Barron E. L. , Sosnovtsev S. V. , Green K. Y. . ( 2006; ). Pathology of immunodeficient mice with naturally occurring murine norovirus infection. . Toxicol Pathol 34:, 708–715. [CrossRef] [PubMed]
    [Google Scholar]
  41. Wirtz S. , Neufert C. , Weigmann B. , Neurath M. F. . ( 2007; ). Chemically induced mouse models of intestinal inflammation. . Nat Protoc 2:, 541–546. [CrossRef] [PubMed]
    [Google Scholar]
  42. 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]
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