Enhanced replication of herpes simplex virus type 1 in human cells

• Published in: Journal of dental research Vol. 70; no. 2; p. 111
• Main Authors: Miller, C S, Smith, K O
• Format: Journal Article
• Language: English
• Published: United States 01-02-1991
• Subjects: Cell Line; DNA Damage; DNA Repair - drug effects; DNA Repair - radiation effects; DNA Replication - drug effects; DNA Replication - radiation effects; DNA, Viral - drug effects; DNA, Viral - radiation effects; Fibroblasts - metabolism; Fibroblasts - microbiology; Gamma Rays; Humans; Lung - cytology; Methyl Methanesulfonate - analogs & derivatives; Methyl Methanesulfonate - pharmacology; Simplexvirus - genetics; Simplexvirus - growth & development; Time Factors; Ultraviolet Rays; Viral Plaque Assay; Virus Activation - drug effects; Virus Activation - radiation effects
• ISSN: 0022-0345
• DOI: 10.1177/00220345910700020301

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.