Herpes Simplex Virus Neurovirulence Across the Human Lifespan

The ability of herpes simplex virus (HSV) to establish lifelong latency in sensory neurons makes it one of the most pervasive viruses worldwide. Although most HSV infections are asymptomatic or cause limited cutaneous symptoms, some give rise to serious central nervous system (CNS) manifestations. Both primary HSV infection and subsequent reactivation events can cause viral replication and spread within the brain, ultimately leading to pathologic inflammation and direct CNS damage. In addition to fulminant presentations of HSV encephalitis, subclinical HSV CNS infections have been implicated in neurodevelopmental, cognitive, and neurodegenerative impairment. Here, we review the pathogenesis of HSV infection and resulting CNS manifestations across the human lifespan. Identifying the mechanisms of HSV-induced CNS damage, and therefore the populations at highest risk for neurological morbidity, may provide a better understanding of the role viruses play in neurological diseases and inform novel approaches to treatment.