Further evidence from a murine infection model that famciclovir interferes with the establishment of HSV-1 latent infections

Abstract

Mice were infected with herpes simplex virus type 1 (HSV-1) via the ear pinna. Famciclovir therapy was commenced on days 2-7 post infection (p.i.). The ipsilateral and contralateral trigeminal (TG) and third cervical ganglia (CIII) from individual mice were tested for latency 1 and 6 months after infection by explant culture or in situ hybridization for latency-associated transcripts (LAT). There were significantly fewer LAT-positive neurons in ipsilateral and contralateral TG (but not CIII) when therapy was delayed by up to 6 days. There was a low correlation between the number of LAT-positive neurons and reactivation by explant culture. Latency data for individual ganglia, compared with those from previous studies, allow us to rationalize differences between the effects of nucleosides on the establishment of latency in different anatomical sites and when tissues are evaluated using different techniques. The implications of the findings for the use of famciclovir to counter HSV latency in humans are addressed.