Mutagenesis occurring following infection with herpes simplex virus does not require virus replication

Area of Science:

• Molecular Biology
• Virology
• Genetics

Background:

• Herpes simplex virus (HSV) infection is known to affect cellular processes.
• Previous studies suggest HSV infection can increase mutation rates in host cells.

Purpose of the Study:

• To investigate the mutagenic potential of HSV-1 and HSV-2 infection in eukaryotic cells.
• To determine if the expression of HSV ribonucleotide reductase (RR) contributes to viral mutagenesis.
• To identify the viral components responsible for the observed increase in mutation frequency.

Main Methods:

• Infection of cultured eukaryotic cells with HSV-1 and HSV-2.
• Construction of plasmids to express HSV-2 ribonucleotide reductase subunits.
• Use of HSV-1 temperature-sensitive mutants and UV-inactivated virus to pinpoint mutagenic factors.

Main Results:

• HSV-1 and HSV-2 infection increased the mutation frequency of a shuttle vector gene by approximately sixfold.
• Expression of HSV-2 ribonucleotide reductase subunits did not affect mutation frequency.
• Mutagenic effects were observed regardless of viral replication or gene expression, and with temperature-sensitive mutants.

Conclusions:

• HSV infection exerts a significant mutagenic effect on eukaryotic cells.
• Viral replication and gene expression are not required for this mutagenic effect.
• The findings suggest that HSV may contribute to cellular transformation through non-productive infections.