Activation of herpes simplex virus (HSV) type 1 genome by temperature-sensitive mutants of HSV type 2.
Previous studies have demonstrated that herpes simplex viruses (HSV) type 1 (HSV-1) and type 2 (HSV-2) can be maintained in a repressed form in human embryo lung cells. Reducing the incubation temperature or superinfecting with a heterologous herpesvirus, human cytomegalovirus (HCMV), results in activation of virus replication. We now report that superinfection with a partially homologous herpesvirus, HSV-2, also resulted in activation of HSV-1. To minimize excessive synthesis of infectious HSV-2 while allowing virus gene expression, repressed HSV-l-infected cultures were superinfected with HSV-2 temperature-sensitive (ts) mutants (tsF3, tsB5, or tsH9). The predominant virus replicated after HSV-2 ts mutant superinfection at a nonpermissive temperature was identified as activated parental-like HSV-1 by (i) plaquing efficiency at permissive (34 degrees) and nonpermissive (40.5 degrees) temperatures, (ii) sensitivity to inhibition by the HSV-l-specific antiviral agent (E)-5-(2-bromovinyl)-2'-deoxyuridine, and (iii) restriction endonuclease cleavage analysis. In addition, the fact that superinfection with HSV-2 tsB5 or tsH9, which are unable to synthesize virus DNA and express only early virus genes at nonpermissive temperature, resulted in synthesis of virus demonstrated that HSV-2 DNA synthesis is not required for activation. This system has provided the basis for further studies concerning the regulation of HSV gene expression in human cells.
D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000494:pharmacology; D003587:Cytomegalovirus / Q000254:growth & development; D004262:DNA Restriction Enzymes; D004279:DNA, Viral / Q000032:analysis; D005814:Genes, Viral; D007700:Kinetics; D009154:Mutation; D018139:Simplexvirus / Q000235:genetics / Q000254:growth & development*; D013696:Temperature; D010948:Viral Plaque Assay; D014775:Virus Activation; D014776:Virus Cultivation; D014779:Virus Replication / Q000187:drug effects
D004279:DNA, Viral; C020235:brivudine; D004262:DNA Restriction Enzymes; D001973:Bromodeoxyuridine