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Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains.


ABSTRACT:

Background

The polymorphisms involved in drug resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1 CRF_BC, the most prevalent HIV-1 strain in China, have been poorly characterized.

Results

To reveal the drug resistance mutations, we compared the gene sequences of pol region of HIV-1 CRF_BC from 631 treatment-naïve and 363 treatment-experienced patients using the selection pressure-based method. We calculated an individual Ka/Ks value for each specific amino acid mutation. Result showed that eight polymorphic mutations (W88C, K101Q, I132L, R135L, T139K/R, H221Y and L228R) in RT for treatment-experienced patients were identified, while they, except for R135L, were completely absent in those from treatment-naïve patients. The I132L and T139K/R mutants exhibited high-level resistance to DLV and NVP and moderate resistance to TMC-125 and EFV, while the K101Q and H221Y mutants exhibited an increased resistance to all four NNRTIs tested. The W88C, R135L, and L228R may be RTI-induced adaptive mutations. Y181C+K101Q mutant showed a 2.5-, 4.4-, and 4.7-fold higher resistance to TMC-125, NVP and EFV, respectively, than Y181C alone mutant, while Y181C+H221Y or K103N+H221Y mutants had significantly higher resistance to all four NNRTIs than Y181C or K103N mutants. K103N+T139K and G190A+T139K mutant induce higher resistance (2.0?14.2-fold and 1.5?7.2-fold, respectively) to all four NNRTIs than K103N or G190A alone mutation.

Conclusions

I132L and T139K/R are rare but critical mutations associated with NNRTI-resistance for some NNRTIs. K101Q, H221Y and T139K can enhance K103N/Y181C/G190A-assocated NNRTI-resistance. Monitoring these mutations will provide useful information for rational design of the NNRTI-based antiretroviral regimen for HIV-1 CRF_BC-infected patients.

SUBMITTER: Huang Y 

PROVIDER: S-EPMC3990534 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains.

Huang Yang Y   Li Zhenpeng Z   Xing Hui H   Jiao Yang Y   Ouyang Yabo Y   Liao Lingjie L   Jiang Shibo S   Armstrong Rebecca R   Shao Yiming Y   Ma Liying L  

PloS one 20140417 4


<h4>Background</h4>The polymorphisms involved in drug resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) in HIV-1 CRF_BC, the most prevalent HIV-1 strain in China, have been poorly characterized.<h4>Results</h4>To reveal the drug resistance mutations, we compared the gene sequences of pol region of HIV-1 CRF_BC from 631 treatment-naïve and 363 treatment-experienced patients using the selection pressure-based method. We calculated an individual Ka/Ks value for each specific am  ...[more]

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