Herpes simplex type 1 infects and establishes latency in the brain and trigeminal ganglia during primary infection of the lip in cotton rats and mice.

The majority of the human population has been infected with herpes simplex virus type 1 (HSV-1). During a typical primary episode, HSV-1 spreads from the oral pharynx to the trigeminal ganglia, where a latent HSV-1 infection is established. Cold sores at the mucocutaneous junction of the lip are the typical manifestation of recurrent HSV-1. We investigated whether HSV-1 also infects the brain during the primary infection. We used HSV-1 infected BALB/c mice and inbred cotton rats as models. While both species were susceptible to HSV-1 infection, the time course of lesion formation and healing in the cotton rat more closely reflected that seen in humans. In both species, HSV-1 replicated in the brainstem and cerebellum, as well as the trigeminal ganglia during a primary infection of the lip. The brain infection was produced by a low inoculation dose, and did not cause observable neurologic signs or mortality. Using PCR and RT-PCR techniques, we demonstrated HSV-1 thymidine kinase in the absence of infectivity in the brains of both species 30-40 days after primary infection.