Disease and latency characteristics of clinical herpes virus isolated after acyclovir therapy.
Herpes simplex virus (HSV) type 1 from a bone marrow transplant recipient and HSV type 2 from a patient with genital herpes infection were examined for sensitivity to acyclovir after both patients received therapy with the drug. A 38- and 83-fold shift in sensitivity was detected in association with a marked decrease in viral thymidine kinase activity in isolates from both patients. The resistant HSV-1 isolate was approximately 900 times less neurovirulent to Balb/C mice but had similar cutaneous virulence in hairless mice compared with the patient's sensitive strain. In contrast, there was no difference in pathogenicity between the sensitive and resistant HSV-2 isolates. Latency was detected in the trigeminal ganglia of mice after snout inoculation with both the sensitive and resistant HSV-1 isolates. The ganglion isolate from the resistant HSV-inoculated mouse was found to be sensitive to acyclovir, implying a selection for or reversion of the sensitive phenotype. No trigeminal ganglion latency was detected after inoculation with either HSV-2 isolate. Resistance to acyclovir can arise during therapy as a result of diminished viral thymidine kinase activity but does not appear to be associated with increased virulence.
D000212:Acyclovir; D000328:Adult; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D004352:Drug Resistance, Microbial; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006558:Herpes Genitalis / Q000188:drug therapy; D006560:Herpes Labialis / Q000188:drug therapy; D006561:Herpes Simplex / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D008297:Male; D051379:Mice; D018139:Simplexvirus / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology; D013283:Stomatitis, Herpetic / Q000188:drug therapy; D013937:Thymidine Kinase / Q000378:metabolism
D000998:Antiviral Agents; D006147:Guanine; D013937:Thymidine Kinase; D000212:Acyclovir