Persistent enteric murine norovirus infection is associated with functionally suboptimal virus-specific CD8 T cell...

Area of Science:

• Immunology
• Virology
• Gastroenterology

Background:

• Norovirus (NV) gastroenteritis causes significant global illness, but immune control mechanisms remain unclear.
• T cells are known to play a role in clearing murine norovirus (MNV), but details of the response are lacking.

Purpose of the Study:

• To investigate the magnitude, location, and dynamics of MNV-specific T cell responses.
• To compare T cell responses to acute (MNV-CW3) versus persistent (MNV-CR6) MNV infection.

Main Methods:

• Identified immunodominant MNV epitopes using overlapping peptide screening.
• Tracked MNV-specific CD8 T cells using MHC class I peptide tetramers in lymphoid and mucosal sites.
• Analyzed T cell activation, differentiation, and homing markers.

Main Results:

• Enteric MNV infection induced strong T cell responses, predominantly in the intestinal mucosa.
• MNV-specific CD8 T cells showed dynamic changes in surface molecule expression.
• Chronic MNV-CR6 infection led to fewer, less functional CD8 T cells compared to acute MNV-CW3 infection, detectable by day 8.
• CD8 T cells reduced viral load in persistently infected mice.

Conclusions:

• CD8 T cells are critical for controlling norovirus infection, particularly within the intestinal mucosa.
• Distinct MNV strains elicit different CD8 T cell responses, impacting viral clearance.
• These findings advance understanding of adaptive immunity to norovirus and protective antiviral responses in the gut.