The TRiC chaperonin controls reovirus replication through outer-capsid folding

Area of Science:

• Virology
• Molecular Biology
• Cell Biology

Background:

• Viruses rely on host cell machinery for replication, with many cellular factors involved in the viral life cycle.
• Understanding virus-host interactions is crucial, especially for late-stage replication events.
• The T-complex protein-1 (TCP-1) ring complex (TRiC), a molecular chaperone, has been implicated in various cellular protein folding pathways.

Purpose of the Study:

• To identify cellular factors essential for late-stage replication of mammalian reovirus.
• To elucidate the specific role of TRiC in the reovirus infectious cycle.
• To explore the potential of TRiC as a target for antiviral therapies.

Main Methods:

• RNA interference (RNAi) screening to identify host factors involved in reovirus replication.
• Biochemical assays to analyze protein folding and complex formation.
• Analysis of viral capsid protein assembly in the presence and absence of TRiC function.

Main Results:

• TRiC was identified as a critical cellular factor required for late stages of reovirus replication.
• TRiC facilitates the correct folding of the viral σ3 outer-capsid protein, enabling its assembly onto progeny virions.
• TRiC also interacts with capsid proteins of related viruses, suggesting a conserved mechanism.

Conclusions:

• TRiC plays a vital role in the viral assembly process, specifically in folding key capsid proteins.
• The mechanism involving TRiC in reovirus assembly may be conserved among related non-enveloped viruses.
• TRiC represents a promising target for the development of novel small-molecule antiviral drugs.