Herpes simplex virus (HSV) establishes a latent infection in the human
peripheral nervous system and can cause recurrent disease by reactiva
tion. Intensive effort has been directed in recent years to unveil the
molecular, cellular and immune mechanisms, as well as the virus-host
interactions associated with latent HSV infection. The aim of this rev
iew is to summarize current knowledge regarding the site of latent inf
ection, the molecular phenomena of latency, and the mechanisms of the
various stages of HSV-1 latent infection in the nervous system, relati
ng them where possible to the human situation. Specifically, the follo
wing biological questions are addressed: (1) How does this lytic virus
survive in the nervous system and why can it establish a lifelong lat
ent infection in nerve cells? (2) What advantage is conferred on HSV b
y establishing latent infection in nervous tissue? (3) What can be gat
hered from the accumulated knowledge on latency about the pathogenesis
of herpes simplex encephalitis?