MUTAGENESIS OCCURRING FOLLOWING INFECTION WITH HERPES-SIMPLEX VIRUS DOES NOT REQUIRE VIRUS-REPLICATION

Infection of eukaryotic cells in culture with herpes simplex virus type-1 (HSV-1) or HSV-2 increased the mutation frequency of the supF gene carried on the shuttle vector pZ189 by around sixfold. The increase was apparent 2 hr postinfection and reached a peak after 8 hr. To investigate this mutagenesis, plasmids pCKRR1 and pCKRR2 were constructed to express the large and small subunits, respectively, of HSV-2 ribonucleotide reductase (RR) under the control of the inducible mouse metallothionein promoter. Expression from these plasmids, either singly or together, had no effect on the mutation frequency of pZ189 under conditions when virus RR activity was detected. The HSV-1 temperature sensitive (ts) mutant viruses ts1207 and ts1222, which have ts lesions in the genes encoding R1 and R2, respectively, were as mutagenic as wild-type HSV-1 at both the permissive and nonpermissive temperatures. These results indicate that expression of HSV RR is not mutagenic in this system. Experiments using other HSV-1 mutants and ultraviolet-inactivated virus localized the cause of the increased mutagenic frequency either to a component of the incoming virion or to an effect exerted by the virus DNA itself. The present study confirms previous reports that infection with HSV exerts a mutagenic effect. Further, virus replication and gene expression were not required for the mutagenic effect studied here. This may have implications for a role of HSV in cellular transformation, as a nonproductive infection could mutagenize cellular genes. © 1991.