Cellular stress rather than stage of the cell cycle enhances the replication and plating efficiencies of herpes simplex virus type 1 ICP0- viruses

This lab reported previously that the plating efficiency of a herpes simplex virus type 1. ICPO-null mutant was enhanced upon release from an isoleucine block which synchronizes cells to G, phase (W. Cai and P. A. Schaffer, J. Virol. 65:4078-4090,1991). Peak plating efficiency occurred as cells cycled out of G, and into S phase, suggesting that the enhanced plating efficiency was due to cellular activities present in late G(1)/early S phase. We have found, however, that the enhanced plating efficiency did not occur when cells were synchronized by alternative methods. We now report that the plating efficiency of ICP0(-) viruses is not enhanced at a particular stage of the cell cycle but rather is enhanced by specific cellular stresses. Both the plating and replication efficiencies of ICPO- viruses were enhanced as much as 25-fold to levels similar to that of wild-type virus when monolayers were heat shocked prior to infection. In addition to heat shock, UV-C irradiation but not cold shock of monolayers prior to infection resulted in enhanced plating efficiency. We further report that the effect of cellular stress is transient and that cell density rather than age of the monolayers is the primary determinant of ICP0- virus plating efficiency. As both cell stress and ICP0 are required for efficient reactivation from latency, the identification of cellular activities that complement ICP0- viruses may lead to the identification of cellular activities that are important for reactivation from neuronal latency.