Journal of Dental Research, Vol 70, 111-117, Copyright © 1991 by International & American Associations for Dental Research Online Journals
Enhanced replication of herpes simplex virus type 1 in human cells
C. S. Miller and K. O. Smith
Department of Oral Health Science, MN228 Chandler Medical Center, University of Kentucky College of Dentistry, Lexington 40536.
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.
