Molecular and biological characterization of a type 1 herpes simplex virus (HSV-1) specifically deleted for...

We have previously reported that in sensory neurons of mice harboring latent herpes simplex virus (HSV), a novel virus-encoded RNA species termed the latency-associated transcript (LAT) is abundant. To investigate a potential function for LAT in the latent state, we have engineered a deletion in HSV-1 strain KOS(M) which abolishes LAT expression. The deletion virus (KOS 8117) is not altered for virulence or the ability to replicate in mouse cells in vivo or in vitro. Although no transcripts were detected in lumbosacral ganglia of mice after virus inoculation on scarified rear footpads, the deletion virus established a latent infection since infectious virus could be recovered by explanting and cultivating ganglia in vitro with permissive cells. These results indicate that expression of LAT is not an absolute requirement for the establishment or maintenance of the latent state or for recovery of infectious virus from the latent state by in vitro co-cultivation. Since no viral-encoded transcripts were detected in cells latently infected with KOS 8117, maintenance of the latent infection also appears to be exclusively a neuronal function.