کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3427647 1227430 2006 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNALys, 3 that correlate with reductions in replication
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
پیش نمایش صفحه اول مقاله
The HIV-1 reverse transcriptase mutants G190S and G190A, which confer resistance to non-nucleoside reverse transcriptase inhibitors, demonstrate reductions in RNase H activity and DNA synthesis from tRNALys, 3 that correlate with reductions in replication
چکیده انگلیسی

We evaluated the replication efficiency of the HIV reverse transcriptase (RT) mutants K103N, G190A, and G190S, which confer resistance to the non-nucleoside RT inhibitor efavirenz, using growth competition assays in cell culture. In the absence of efavirenz, the fitness hierarchy was G190S < G190A < K103N < wild-type. The fitness reduction of G190S relative to K103N was less evident at high efavirenz concentrations, although K103N still replicated more efficiently. Efficiency of RNase H cleavage and RNA-dependent DNA synthesis from tRNALys, 3 correlated with relative fitness, in biochemical studies of mutant RTs. Presteady state and steady state polymerization assays using DNA primers detected no abnormalities. This work is consistent with previous studies demonstrating that initiation of viral DNA synthesis is reduced in mutants with slowed RNase H cleavage, and suggests that both abnormalities contribute to the replication defect of these mutants. It also suggests that high concentrations of efavirenz are unlikely to favor the selection of G190S clinically.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virology - Volume 348, Issue 2, 10 May 2006, Pages 462–474
نویسندگان
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