CAPRIN1 Is Required for Control of Viral Replication Complexes by Interferon Gamma

Area of Science:

• Virology
• Cellular Biology
• Immunology

Background:

• Positive-strand RNA viruses form replication complexes (RCs) using host membranes to shield viral RNA from immune defenses.
• Autophagy and interferon (IFN) pathways are conserved defense systems that work together to inhibit viral replication by targeting RCs.
• The precise mechanisms by which autophagy proteins and IFN-inducible GTPases disrupt viral RCs are not fully understood.

Purpose of the Study:

• To elucidate the mechanism of autophagy-mediated targeting of viral replication complexes.
• To identify the specific IFN-inducible GTPase involved in inhibiting viral RCs.
• To understand the role of autophagy proteins in the recognition and disruption of viral RCs.

Main Methods:

• Utilized murine norovirus (MNV) as a model (+) RNA virus.
• Investigated the function of guanylate binding protein 1 (GBP1) in inhibiting RCs.
• Examined the interaction of ATG16L1 with WIPI2B and CAPRIN1 for LC3 targeting of RCs.
• Assessed the dependency of IFN gamma-mediated control of MNV replication on CAPRIN1.

Main Results:

• Identified guanylate binding protein 1 (GBP1) as the sole GTPase responsible for inhibiting viral replication complexes (RCs).
• Demonstrated that ATG16L1 mediates LC3 targeting of MNV RCs by interacting with WIPI2B and CAPRIN1.
• Established that IFN gamma-induced inhibition of MNV replication is dependent on the protein CAPRIN1.

Conclusions:

• Uncovered a novel mechanism where the autophagy machinery recognizes and inhibits viral RCs, a key feature of (+) RNA virus replication.
• Identified GBP1 as the specific guanylate-binding protein targeting viral RCs.
• Revealed a new role for CAPRIN1 in recruiting ATG16L1 to viral RCs, facilitating their disruption.