HSV targeting of the host phosphatase PP1α is required for disseminated disease in the neonate and contributes to pathogenesis in the brain

Significance The increased severity of herpes simplex virus (HSV) disease in the newborn compared with the adult is a result of complex interactions between the virus and the host response. We studied viral targeting of host-mediated shutoff of protein synthesis during HSV disease in a murine model and found that HSV-1 targeting of the host phosphatase PP1α was required for disseminated disease in the newborn and contributed to HSV encephalitis. Additionally, this report demonstrates that the host response resulting in translational arrest is tissue-specific and also reveals a tissue-specific reliance on the type I IFN response for control of HSV-1. These results provide important insight into the mechanisms of severe HSV disease in the newborn compared with the adult.