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Characterization of the DNA polymerase gene of varicella-zoster viruses resistant to acyclovir

Department of Virology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan¹

Author for correspondence: Kimiyasu 4. Fax +81 76 434 5020. e-mail kshiraki{at}toyama-mpu.ac.jp

The nucleotide changes of the DNA polymerase gene and the susceptibility of acyclovir (ACV)-resistant varicella-zoster virus (VZV) mutants to anti-herpetic drugs were determined and compared to those of herpes simplex virus type 1 (HSV-1) mutants. The seven ACV-resistant VZV mutants were classified into three groups, N⁷⁷⁹S, G⁸⁰⁵C and V⁸⁵⁵M, according to the sequences of their DNA polymerase genes. The amino acid substitutions N⁷⁷⁹S and G⁸⁰⁵C were identical in position to the N⁸¹⁵S and G⁸¹⁴C mutations in the HSV-1 DNA polymerase mutants, respectively, and the V⁸⁵⁵M amino acid substitution was similar to the HSV-1 V⁸⁹²M mutation. All three groups of VZV mutants were susceptible to ACV, phosphonoacetic acid, vidarabine and aphidicolin, at levels similar to those seen with the respective HSV-1 mutants, except for subtle differences that were due possibly to the non-conserved regions in their sequences. Although both the HSV-1 and the VZV DNA polymerase genes show 53% sequence similarity, both viruses essentially show a similar biochemical behaviour.

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