Pathology caused by persistent murine norovirus infection

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.