Antiviral drug resistance.
Antiviral drug resistance is an area of increasing importance in acquired immunodeficiency syndrome (AIDS), not only in terms of the human immunodeficiency virus (HIV), but also opportunistic pathogens such as herpes simplex virus (HSV) and human cytomegalovirus (CMV). Studies of drug resistance in these and other viruses have proven valuable both for the molecular dissection of drug mechanisms and drug targets and for predicting the features of drug resistance in clinical settings: Drug-resistance mutations arise readily, due in part to a lack of fidelity of viral polymerase. Both biochemical and genetic analyses are generally required to understand the basis of drug resistance. Novel drug targets, such as a CMV gene product that contributes to ganciclovir phosphorylation, can be identified by analysis of such mutations. Regions of drug targets that are involved in drug recognition can be identified by sequencing of drug-resistance mutations. Analysis of drug-resistant viruses, obtained either in the laboratory or from patients, reveals a broad spectrum of alterations and points to the importance of heterogeneous populations of virus in resistance and pathogenesis.
Coen
D M
DM
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004352:Drug Resistance, Microbial / Q000235:genetics; D006678:HIV / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006564:Herpesviridae / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007108:Immune Tolerance; D009154:Mutation; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism
D000998:Antiviral Agents; D012194:RNA-Directed DNA Polymerase; D004259:DNA-Directed DNA Polymerase