DNA mismatch repair proteins are required for efficient herpes simplex virus 1 replication

Area of Science:

• Virology
• Molecular Biology
• DNA Repair

Background:

• Herpes simplex virus 1 (HSV-1), a DNA virus, interacts with host cell DNA repair proteins during replication.
• Cellular mismatch repair (MMR) proteins are essential for maintaining genomic integrity.

Purpose of the Study:

• To investigate the role of MMR proteins, specifically MSH2 and MLH1, in the HSV-1 life cycle.
• To determine the specific functions and timing of MMR protein involvement in viral replication.

Main Methods:

• Co-immunoprecipitation assays to confirm protein interactions.
• Localization studies using microscopy to track protein recruitment to viral replication sites.
• Gene knockdown experiments (MLH1, MSH2) to assess effects on viral gene expression and replication.

Main Results:

• Both MLH1 and MSH2 are required for efficient HSV-1 replication and localize to viral replication compartments.
• MLH1 associates with ND10 nuclear bodies and is recruited to the incoming viral genome, inhibiting immediate-early gene expression upon knockdown.
• MSH2 is not recruited to incoming genomes and acts at a later stage, with its silencing inhibiting early gene expression.

Conclusions:

• MLH1 and MSH2 participate in distinct, essential events during the HSV-1 life cycle.
• MLH1's early role in HSV-1 infection is surprising and suggests a function beyond its known MSH2-dependent MMR role.