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Journal of Dental Research
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Enhanced Replication of Herpes Simplex Virus Type 1 in Human Cells

C.S. Miller

Department of Oral Health Science, Division of Oral Diagnosis, MN228 Chandler Medical Center, University of Kentucky College of Dentistry, Lexington, Kentucky 40536

K.O. Smith

Department of Microbiology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78284

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 < 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<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 eenomes.

Journal of Dental Research, Vol. 70, No. 2, 111-117 (1991)
DOI: 10.1177/00220345910700020301
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C.S. Miller, R.J. Danaher, and R.J. Jacob
Molecular Aspects of Herpes Simplex Virus I Latency, Reactivation, and Recurrence
Critical Reviews in Oral Biology & Medicine, January 1, 1998; 9(4): 541 - 562.
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