Manipulation of the Host DNA Damage Response by Herpes Simplex Virus

Despite the fact that the cis- and trans-acting factors required for Herpes Simplex Virus DNA replication were identified almost 30 years ago, little is known about the actual mechanisms of HSV DNA replication. It has become clear that in order to establish a lytic infection, HSV must counteract intrinsic antiviral mechanisms that are activated upon infection. HSV has evolved to inactivate specific components of all three major DNA damage sensing pathways, DNA-PK, ATM and ATR, in order to create an environment conducive for productive viral replication. Several viral proteins are required to guide pathway choices that result in the generation of progeny DNA genomes that can be packaged into infectious virions.