The effect of cellular DNA repair factors on HSV-1 recombination

Herpesviridae is a family of large double strand DNA viruses that replicates in the cell`s nucleus. An important member of this family is Herpes Simplex Virus 1 (HSV-1) which is studied as a model for viral DNA replication. In HSV-1, recombination among co-infecting genomes is a frequent event, suggesting recombination is key driver of viral evolution. Both homologous and non-homologous recombination are observed during infection but little is known about the mechanism. While HSV-1 encodes its own replication and recombination proteins, it is suggested that host proteins are also involved in these processes. We hypothesize that viral recombination is regulated by host cellular DNA repair factors. To test the hypothesis, we performed targeted siRNA screen against host cellular DNA repair factors. Homologous and non-homologous recombination rates were measured by monitoring progeny viruses from coinfection with two different HSV-1 recombinants each carry different fluorescent reporter genes. Our screens identify differences in both homologous and non-homologous recombination rates after treatment with siRNA, when compared to the control. This suggests that cellular DNA repair factors take a role in HSV-1 recombination process and can help understand the mechanism behind this process.