Analysis of the thymidine kinase gene from clinically isolated acyclovir-resistant herpes simplex viruses.
The isolation and description of acyclovir-resistant (ACVR) herpes simplex-2 viruses from patients with AIDS has recently been reported. These ACVR viruses were all markedly decreased in their thymidine kinase (TK) activity, and 6 of 10 of these TK viruses were able to establish latency. In addition, one of these isolates, ACVR-86012 was neuropathogenic in a murine encephalitis model. In this paper, the characteristics of these isolates with respect to TK polypeptide synthesis are examined. All but one isolate synthesized a detectable TK protein by immunoprecipitation, and 9/10 of the TK proteins had an altered electrophoretic mobility as compared to wild-type. The TK polypeptide from the neuropathogenic isolate ACVR-86012 was full-length and the gene was sequenced. An amino acid change from a glutamine to a proline at amino acid residue 105 was detected compared to the wild-type HSV-333 strain. These results indicate that an amino acid change in the NH2 portion of the TK protein is associated with a full-length peptide with decreased enzyme activity but the virus retains neuropathic virulence.
Chatis
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Division of Infectious Diseases, Beth Israel Hospital, Harvard Medical School, Boston, Massachusetts 02215.
Crumpacker
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CS
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000382:microbiology; D000212:Acyclovir / Q000494:pharmacology*; D004352:Drug Resistance, Microbial / Q000235:genetics; D005814:Genes, Viral; D006801:Humans; D018139:Simplexvirus / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D013937:Thymidine Kinase / Q000235:genetics*; D010948:Viral Plaque Assay; D015678:Viral Structural Proteins / Q000235:genetics*
D015678:Viral Structural Proteins; D013937:Thymidine Kinase; D000212:Acyclovir