Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains.
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 reg...
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| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3990534?pdf=render |
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| author | Yang Huang Zhenpeng Li Hui Xing Yang Jiao Yabo Ouyang Lingjie Liao Shibo Jiang Rebecca Armstrong Yiming Shao Liying Ma |
| author_facet | Yang Huang Zhenpeng Li Hui Xing Yang Jiao Yabo Ouyang Lingjie Liao Shibo Jiang Rebecca Armstrong Yiming Shao Liying Ma |
| author_sort | Yang Huang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-23T14:58:18Z |
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| id | doaj.art-f54988dae8e44829aecbfd9d8e2961e1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-23T14:58:18Z |
| publishDate | 2014-01-01 |
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| spelling | doaj.art-f54988dae8e44829aecbfd9d8e2961e12022-12-21T17:42:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9380410.1371/journal.pone.0093804Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains.Yang HuangZhenpeng LiHui XingYang JiaoYabo OuyangLingjie LiaoShibo JiangRebecca ArmstrongYiming ShaoLiying MaBACKGROUND: 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.http://europepmc.org/articles/PMC3990534?pdf=render |
| spellingShingle | Yang Huang Zhenpeng Li Hui Xing Yang Jiao Yabo Ouyang Lingjie Liao Shibo Jiang Rebecca Armstrong Yiming Shao Liying Ma Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. PLoS ONE |
| title | Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. |
| title_full | Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. |
| title_fullStr | Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. |
| title_full_unstemmed | Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. |
| title_short | Identification of the critical sites of NNRTI-resistance in reverse transcriptase of HIV-1 CRF_BC strains. |
| title_sort | identification of the critical sites of nnrti resistance in reverse transcriptase of hiv 1 crf bc strains |
| url | http://europepmc.org/articles/PMC3990534?pdf=render |
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