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Vol 44(2010) N 3 p. 431-438;
A.N. Korovina1*, A.A. Guskova2, M.Y. Skoblov2, V.L. Andronova3, G.A. Galegov3, S.N. Kochetkov1, М.К. Куханова1, Y.S. Skoblov4

Mutations in the DNA Polymerase and Thymidine Kinase Genes of Herpes Simplex Virus Clinical Isolates Resistant to Antiherpetic Drugs

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991 Russia
2Research Centre for Medical Genetics, Russian Academy of Medical Sciences, Moscow, 115478 Russia
3Ivanovskii Institute of Virology, Russian Academy of Medical Sciences, Moscow, 123098 Russia
4Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997 Russia

*anna.korovina@gmail.com
Received - 2009-10-09; Accepted - 2009-11-19

Primary structures of DNA polymerase (ul30) and thymidine kinase (ul23) genes from several herpes simplex virus type 1 (HSV-1) clinical isolates differing in sensitivity to several antiherpetic drugs were determined and compared to those of two laboratory HSV-1 strains one of which (L2) was sensitive and the other (L2/R) was resistant to acyclovir. The phylogenetic sequence analysis showed that the ul30 and ul23sequences of clinical isolates were close to those of L2, and that ul30 conserved regions differed between HSV-1 isolates and L2 only in point mutations and degenerated substitutions. Several new mutations in the HSV-1 DNA polymerase and thymidine kinase functional domains were identified as substitutions associated with strain resistance to ACV and other antiherpetic drugs.

DNA polymerase, thymidine kinase, drug resistance, herpes simplex virus, primary structure



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