Norovirus co-opts NINJ1 for selective protein secretion

Area of Science:

• Virology
• Cell Biology
• Immunology

Background:

• Ninjurin-1 (NINJ1) mediates programmed cell death via plasma membrane rupture, releasing damage-associated molecular patterns (DAMPs).
• The regulation and selectivity of NINJ1-mediated DAMP release are not well understood.
• Murine norovirus (MNoV) infection involves complex host-pathogen interactions at the cellular level.

Purpose of the Study:

• To investigate the role of NINJ1 in MNoV infection and viral protein release.
• To understand the mechanisms regulating NINJ1-mediated release of intracellular viral components.
• To identify host factors essential for MNoV NS1 secretion.

Main Methods:

• CRISPR screening to identify host factors for NS1 secretion.
• Mutagenesis studies to analyze NINJ1-NS1 interactions.
• In vivo studies using genetic ablation and pharmaceutical inhibition of caspase-3 in MNoV-infected mice.

Main Results:

• MNoV co-opts NINJ1 for selective release of intracellular viral protein NS1.
• NINJ1 forms speckled bodies at the viral replication site and interacts with NS1.
• Caspase-3 cleavage of NS1 precursor is crucial for its unconventional secretion.
• Inhibition of caspase-3 reduces oral MNoV infection in mice.
• NINJ1-mediated rupture releases both viral NS1 and cellular DAMPs.

Conclusions:

• NINJ1 plays a critical role in the selective release of MNoV NS1.
• MNoV utilizes NINJ1 for controlled release of intracellular viral proteins.
• Caspase-3 is essential for MNoV infection by enabling NS1 secretion.