Herpes simplex virus genes involved in latency in vitro

The properties of temperature-sensitive (ts), insertion or deletion mutants of herpes simplex virus (HSV) were investigated in an in vitro model system for latency. The studies defined virus gene products required for establishment of latency and for reactivation of latent virus. All mutants tested established latency in human foetal lung fibroblasts and could be reactivated by intertypic superinfection with HSV or with human cytomegalovirus. Two mutants of HSV type 1 used in these studies, tsK and in1411, failed to synthesize active immediate early (IE) polypeptide Vmw175 and were blocked at a very early stage of the virus replication cycle, showing that, at most, only limited gene expression is necessary for the establishment of latency. Mutant dl1403, which lacks the gene encoding IE polypeptide Vmw110, established latency as efficiently as wild-type HSV. Latent HSV type 2 was reactivated by superinfection with tsK or in1411 but not with dl1403, suggesting that polypeptide Vmw110, which is known to regulate gene expression by trans-activation, is required for reactivation in the in vitro system.