Mutations in the Exo III motif of the herpes simplex virus DNA polymerase gene can confer altered drug sensitivities

Virology
Y T HwangC B Hwang

Abstract

Two herpes simplex virus mutants containing mutated residues within the conserved Exo III motif of the polymerase gene were previously shown to be defective in 3'-5' exonuclease activity and exhibited extremely high mutation frequencies. In this study, we have shown that these mutants also exhibited higher resistance to phosphonoacetic acid and sensitivity to aphidicolin and all nucleoside analogs tested, including acyclovir and gangciclovir, compared to wild-type virus. Marker transfer experiments and sequencing analyses demonstrated that these altered phenotypes were the result of mutations within the Exo III motif. The data indicate that, aside from leading to exonuclease deficiency, mutations in the Exo III motif may also affect interaction of nucleoside triphosphates with the catalytic sites of polymerase activity.

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Citations

Oct 26, 2000·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Y ChenP Ribaud
Nov 17, 2010·Antimicrobial Agents and Chemotherapy·Jocelyne Piret, Guy Boivin
May 7, 2002·Journal of Virology·Qiaosheng LuCharles B C Hwang
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Nov 26, 2014·Proceedings of the National Academy of Sciences of the United States of America·Han ChenDonald M Coen
Mar 8, 2014·Reviews in Medical Virology·Jocelyne Piret, Guy Boivin
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Jul 9, 2010·Molekuliarnaia biologiia·I A GoncharovaV P Puzyrev

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