Altered Drug Sensitivity, Fitness, and Evolution of Human Immunodeficiency Virus Type 1 with Pol Gene Mutations Conferring Multi-dideoxynucleoside Resistance

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 1998 May 21

PMID 9593005

Citations 41

Authors

Y Maeda

D J Venzon

H Mitsuya

Affiliations

Soon will be listed here.

Abstract

Investigations were done to determine whether the replication kinetics of human immunodeficiency virus (HIV)-1 were altered when the virus acquired a set or subsets of five mutations (A62V, V75I, F77L, F116Y, and Q151M) in the pol gene conferring resistance to multiple dideoxynucleosides. In the absence of drugs, the replication rate of all infectious clones generated was comparable to that of wild type HIV-1. However, in the presence of zidovudine or didanosine, the comparative order for replication was HIV-1(62/75/77/116/151) > HIV-1(77/116/151) > HIV-1(75/77/116/151) approximately HIV-1(151), whereas that for drug resistance was HIV-1(75/77/116/151) > HIV-1(62/75/77/116/151) > or = HIV-1(77/116/151) > HIV-1(151). The virologic features of these infectious mutants suggest that HIV-1 develops drug resistance through one or more mutations, which, however, sacrifice replicative capability; then it finally acquires optimal replication competence by additional mutations when the multi-dideoxynucleoside-resistant mutant emerges.

Citing Articles

The HIV-1 Reverse Transcriptase A62V Mutation Influences Replication Fidelity and Viral Fitness in the Context of Multi-Drug-Resistant Mutations.

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HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir.

Yasutake Y, Hattori S, Hayashi H, Matsuda K, Tamura N, Kohgo S Sci Rep. 2018; 8(1):1624.

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Structural Insights into HIV Reverse Transcriptase Mutations Q151M and Q151M Complex That Confer Multinucleoside Drug Resistance.

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Miyamoto F, Kawaji K, Oishi S, Fujii N, Kaku M, Kodama E Antivir Chem Chemother. 2015; 24(2):77-82.

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