Characterization of a cidofovir-resistant HHV-6 mutant obtained by in vitro selection

被引：20

作者：

Bonnafous, Pascale ^{[1
]}

Boutolleau, David ^{[1
]}

Naesens, Lieve ^{[2
]}

Deback, Claire ^{[1
]}

Gautheret-Dejean, Agnes ^{[1
,3
]}

Agut, Henri ^{[1
]}

机构：

[1] Univ Paris 06, Grp Hosp Pitie Salpetriere, EA2387, F-75013 Paris, France

[2] Katholieke Univ Leuven, Lab Virol & Chemotherapy, Rega Inst Med Res, B-3000 Louvain, Belgium

[3] Fac Sci Pharmaceut & Biol Paris, Microbiol Lab, F-75006 Paris, France

来源：

ANTIVIRAL RESEARCH | 2008年 / 77卷 / 03期

关键词：

HHV-6; cidofovir; resistance; DNA polymerase;

D O I：

10.1016/j.antiviral.2007.12.004

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Cidofovir (CDV) was used for in vitro selection of a human herpesvirus 6 (HHV-6) mutant with decreased susceptibility to this drug. The resulting mutant was highly resistant to CDV as compared to its sensitive counterpart (inhibitory concentration 50% (IC50): 213 mu M versus 1.8 mu M). Its replication fitness was not impaired. Genotypic characterization of the resistant virus revealed a mutation in the U38 gene encoding the viral DNA polymerase. The resulting R798I amino acid change was located in the conserved domain VII close to the highly conserved motif KKRY interacting with the DNA primer-template duplex, and is likely responsible for the high-level resistance to CDV, even though a definite virological and/or biochemical confirmation is required. The possible emergence of such changes in HHV-6 DNA polymerase in patients receiving CDV therapy should be taken into account in the treatment of HHV-6 infections. (C) 2007 Elsevier B.V. All rights reserved.

引用

页码：237 / 240

页数：4

共 26 条

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