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Updated: May 6, 2026
Reverse Genetics Mediated Recovery of Infectious Murine Norovirus
Published on: June 24, 2012
Pathology caused by persistent murine norovirus infection
Amita Shortland1, James Chettle1, Joy Archer1
1Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 OES, UK.
Abstract:
Subclinical infection of murine norovirus (MNV) was detected in a mixed breeding group of WT and Stat1(-/-) 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 Stat1(-/-) mice. Histopathological analysis of tissues from WT, heterozygous and Stat1(-/-) 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 Stat1(-/-) or WT mice, and recapitulated the clinical and pathological picture of the naturally infected colony. Unexpectedly, by day 54 post-infection, 50 % of Stat1(-/-) 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.
Insights
Murine norovirus (MNV) infection in mice revealed persistent infection in wild-type (WT) mice, leading to liver lesions, while Stat1-deficient mice cleared the virus. This highlights MNV persistence mechanisms and STAT1-independent responses.
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- Subclinical infections with murine norovirus (MNV) can occur in mouse colonies without apparent illness.
- The role of STAT1 (Signal Transducer and Activator of Transcription 1) in controlling norovirus infection and persistence is not fully understood.
Purpose of the Study:
- To investigate the pathogenesis and immune response to a naturally occurring, attenuated MNV variant (MNV-O7) in wild-type (WT) and Stat1-deficient (Stat1(-/-)) mice.
- To determine the role of STAT1 in MNV clearance and the development of associated pathology.
Main Methods:
- Isolation and characterization of an infectious molecular clone (MNV-O7) from naturally infected mice.
- Experimental infection of WT, heterozygous, and Stat1(-/-) mice with MNV-O7.
- Histopathological analysis of tissues to assess lesions.
- Monitoring viral clearance and host responses over time.
Main Results:
- MNV-O7 induced subclinical infections in both WT and Stat1(-/-) mice, with no mortality or weight loss.
- Stat1(-/-) mice showed 50% clearance of MNV-O7 by day 54 post-infection.
- WT mice exhibited persistent MNV-O7 infection with associated liver lesions in all infected animals.
- STAT1-dependent responses were not essential for protection against lethal MNV infection.
Conclusions:
- Specific MNV variants can establish long-term persistent infections in WT mice, characterized by persistent inflammation in the liver despite a subclinical presentation.
- STAT1-dependent immune responses are not required for protection against lethal MNV infection, but play a role in viral clearance or control.
- The study elucidates distinct outcomes of MNV infection based on host STAT1 status, contributing to understanding norovirus persistence and host-pathogen interactions.
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