title: Enhanced replication of herpes simplex virus type 1 in human cells.
abstract: The effects of DNA-damaging agents on the replication of herpes simplex virus type 1 (HSV-1) were assessed in vitro. Monolayers of human lung fibroblast cell lines were exposed to DNA-damaging agents (methyl methanesulfonate [MMS], methyl methanethiosulfonate [MMTS], ultraviolet light [UV], or gamma radiation [GR]) at specific intervals, before or after inoculation with low levels of HSV-1. The ability of cell monolayers to support HSV-1 replication was measured by direct plaque assay and was compared with that of untreated control samples. In this system, monolayers of different cell lines infected with identical HSV-1 strains demonstrated dissimilar levels of recovery of the infectious virus. Exposure of DNA-repair-competent cell cultures to DNA-damaging agents produced time-dependent enhanced virus replication. Treatment with agent before virus inoculation significantly (p less than 0.025) increased the number of plaques by 10 to 68%, compared with untreated control cultures, while treatment with agent after virus adsorption significantly increased (p less than 0.025) the number of plaques by 7 to 15%. In a parallel series of experiments, cells deficient in DNA repair (xeroderma pigmentosum) failed to support enhanced virus replication. These results suggest that after exposure to DNA-damaging agents, fibroblasts competent in DNA repair amplify the replication of HSV-1, and that DNA-repair mechanisms that act on a variety of chromosomal lesions may be involved in the repair and biological activation of HSV-1 genomes.
authors.affiliation: Department of Oral Health Science, MN228 Chandler Medical Center, University of Kentucky College of Dentistry, Lexington 40536.
authors.forename: C S
authors.initials: CS
authors.lastname: Miller
authors.forename: K O
authors.initials: KO
authors.lastname: Smith
mesh_terms: D002460:Cell Line; D004249:DNA Damage; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D004279:DNA, Viral / Q000187:drug effects / Q000528:radiation effects; D005347:Fibroblasts / Q000378:metabolism / Q000382:microbiology; D005720:Gamma Rays; D006801:Humans; D008168:Lung / Q000166:cytology; D008741:Methyl Methanesulfonate / Q000031:analogs & derivatives / Q000494:pharmacology; D018139:Simplexvirus / Q000235:genetics / Q000254:growth & development*; D013997:Time Factors; D014466:Ultraviolet Rays; D010948:Viral Plaque Assay; D014775:Virus Activation / Q000187:drug effects / Q000528:radiation effects
chemical_list: D004279:DNA, Viral; C014674:methyl methanethiosulfonate; D008741:Methyl Methanesulfonate