[Resistance of herpes simplex viruses to antiviral drugs].
The nucleoside analog acyclovir is remarkably effective and selective in herpes simplex virus (HSF) infections. Acyclovir inhibits the viral enzyme DNA polymerase. Emergence of acyclovir-resistant HSV mutants occurs in immunocompromised patients, especially those with AIDS. Detection of HSV strains with resistance to antiviral drugs requires rapid in vitro tests to determine the IC50, i.e., the concentration of drug which inhibits viral replication by 50%. Studies of patterns of HSV resistance to the various antiviral agents used in medicine and characterization of mutant HSV strains have shown resistance to be due to loss or modification of the viral enzyme thymidine kinase or to changes in the viral DNA polymerase. The main clinically-significant acyclovir-resistant mutants are thymidine kinase-deficient and retain sensitivity to vidarabine and foscarnet. Development of resistance to both acyclovir and foscarnet due to changes in viral DNA polymerase is considerably less common but emphasizes the urgent need for new antiviral strategies for use in immunocompromised patients.
Scieux
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Laboratoire de Bactériologie-Virologie, Hôpital Saint-Louis, Université Paris VII, France.
Bianchi
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D017088:AIDS-Related Opportunistic Infections / Q000150:complications / Q000188:drug therapy; D000163:Acquired Immunodeficiency Syndrome / Q000150:complications*; D000212:Acyclovir / Q000494:pharmacology* / Q000627:therapeutic use; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D004352:Drug Resistance, Microbial; D017245:Foscarnet / Q000494:pharmacology* / Q000627:therapeutic use; D006561:Herpes Simplex / Q000150:complications / Q000188:drug therapy; D066298:In Vitro Techniques; D018139:Simplexvirus / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000378:metabolism; D014740:Vidarabine / Q000494:pharmacology* / Q000627:therapeutic use
D017245:Foscarnet; D013937:Thymidine Kinase; D004259:DNA-Directed DNA Polymerase; D014740:Vidarabine; D000212:Acyclovir