Huang, J

Wang, M

WU, H

Xu, HF

Zhang, H

ZHANG, X

Zheng, B

PLoS ONE

PubMed

Since the antiretroviral therapy (ART) was introduced to patients infected by human immunodeficiency virus (HIV), the HIV related mortality and morbidity have been significantly reduced. The major obstacle for long-term successful anti-HIV treatment is the emergence of drug resistant mutants. Current data of drug resistance was mainly obtained on HIV-1 subtype B but rarely on non-B virus, even more rare with newly emerged circulating recombinant forms (CRFs). The lack of such data limits the rational management of ART for the increasing number of patients infected by non-subtype B virus. In this study, a HIV-1 CRF07_BC strain CNGZD was isolated from a HIV patient and its genome was sequenced and deposited in GenBank (JQ423923). Potential drug resistant mutants of this CRF07_BC virus strain were selected in PBMCs cultures in the presence of Nevirapine (NVP), which is the most frequently used antiretroviral drug in China. Four combination profiles of mutations were identified in the NVP-selected mutants, which were initiated with A98G, V108I, Y181C and I135T/I382L and followed by more than two other mutations at the end of the selections, respectively. A total of seven previously reported mutations (A98G, V106M, V108I, I135T, Y181C, V189I, K238N) and seven novel mutations (P4H, T48I, I178M, V314A, I382L/V, T386A) in the reverse transcriptase gene were found in these NVP-selected mutants. Phenotypic analysis in the NVP-selected mutants showed that all the mutations, except P4H, contribute to NVP resistance. Among them, V106M and Y181C reduce NVP susceptibility for more than 20-fold, while the other mutations cause less than 20 folds drug resistance. Although the information obtained in this in vitro selection study may not fully cover resistant mutations which will actually occur in patients, it has still provided useful information for rational management of ART in patients infected with HIV CRF_BC subtype

Hao Wu

Hao-Jie Zhang

Xiao-min Zhang

Hui-fang Xu

Ming Wang

Jian-dong Huang

Bo-Jian Zheng

Directory of Open Access Journals

Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro.

HKU Scholars Hub

An automated genotyping system for analysis of HIV-1 and other microbial sequences.

Characterization and structural analysis of novel mutations

Characterization of a virtually full-length human immunodeficiency virus type 1 genome of a prevalent intersubtype (C/B’) recombinant strain in China.

Evaluation of an in-house genotyping resistance test for HIV-1 drug resistance interpretation and genotyping.

Genetic diversity and drug resistance of HIV type 1 circulating recombinant Form_BC among drug users in Guangdong Province.

Genetic diversity of protease and reverse transcriptase sequences in non-subtypeB human immunodeficiency virus type 1 strains: evidence of many minor drug resistance mutations in treatment-naive patients.

Global trends in molecular epidemiology of HIV-1 during 2000–2007.

HIV protocols.

HIV-1 drug resistance mutations: an updated framework for the second decade of HAART.

HIV-1 nomenclature proposal.

Human immunodeficiency virus type 1 mutants resistant to nonnucleoside inhibitors of reverse transcriptase arise in tissue culture.

Identification of gammaretroviruses constitutively released from cell lines used for human immunodeficiency virus research.

Isolation and propagation of HIV-1 on peripheral blood mononuclear cells.

Natural polymorphism in protease and reverse transcriptase genes and in vitro antiretroviral drug susceptibilities of non-B HIV-1 strains from treatment-naive patients.

Parental LTRs Are Important in a Construct of a Stable and Efficient Replication-Competent Infectious Molecular Clone of HIV-1 CRF08_BC.

Role of genetic diversity amongst HIV-1 non-B subtypes in drug resistance: a systematic review of virologic and biochemical evidence.

Susceptibilities of human immunodeficiency virus type 1 enzyme and viral variants expressing multiple resistance-engendering amino acid substitutions to reserve transcriptase inhibitors.

Temporal and spatial dynamics of human immunodeficiency virus type 1 circulating recombinant forms 08_BC and 07_BC in Asia.

The Staden package,

The y271 and i274 amino acids in reverse transcriptase of human immunodeficiency virus-1 are critical to protein stability.

Three generic nevirapinebased antiretroviral treatments in Chinese HIV/AIDS patients: multicentric observation cohort.

TMC278, a next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI), active against wild-type and NNRTI-resistant HIV-1.

http://dx.doi.org/10.1371/journal.pone.0044333

Identification of drug resistant mutations in HIV-1 CRF07_BC variants selected by nevirapine in vitro.

Abstract

Similar works

Full text

Available Versions

Directory of Open Access Journals

HKU Scholars Hub