The herpes simplex virus alkaline nuclease is required to maintain replication fork progression

Herpes simplex virus 1 (HSV-1) is a near-ubiquitous pathogen within the global population, causing a lifelong latent infection with sporadic reactivation throughout the life of the host. Within at-risk and immunocompromised communities, HSV-1 infection can cause serious morbidities including herpes keratitis and encephalitis. With the possibility of herpesviruses to evade established antiviral therapies and there being no approved HSV-1 vaccine, there comes a need to investigate potential targets for intervention against infection and subsequent disease. UL12 is the viral 5'-3' exonuclease, which is required for the production of infectious progeny. In this study, we show that in the absence of UL12, viral replication fork progression is abrogated. These data point to UL12 as an attractive target for intervention, which could lead to better clinical outcomes of HSV-1-associated disease in the future.