Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP
Objective. To clarify the impact of H221Y mutation on drug resistance to NVP. Methods. 646 bp HIV-1 pol gene fragments (from 592 to 1237 nucleotide) with different NNRTIs mutation profiles from AIDS patients receiving antiretroviral therapy containing NVP regimens were introduced into pNL4-3 backbon...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2012-01-01
|
| Series: | AIDS Research and Treatment |
| Online Access: | http://dx.doi.org/10.1155/2012/637263 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832551014443515904 |
|---|---|
| author | Liyan Jiao Hanping Li Lin Li Daomin Zhuang Yongjian Liu Zuoyi Bao Siyang Liu Jingyun Li |
| author_facet | Liyan Jiao Hanping Li Lin Li Daomin Zhuang Yongjian Liu Zuoyi Bao Siyang Liu Jingyun Li |
| author_sort | Liyan Jiao |
| collection | DOAJ |
| description | Objective. To clarify the impact of H221Y mutation on drug resistance to NVP. Methods. 646 bp HIV-1 pol gene fragments (from 592 to 1237 nucleotide) with different NNRTIs mutation profiles from AIDS patients receiving antiretroviral therapy containing NVP regimens were introduced into pNL4-3 backbone plasmid. H221Y and (or) Y181C mutations were reverted to wild type amino acids by site-directed mutagenesis, then strains containing various mutation patterns were packaged. Phenotypic drug resistance was analyzed on TZM-bl cells. Results. 12 strains containing different drug-resistant mutation profiles were constructed, including the K101Q series (K101Q/Y181C/H221Y, K101Q/Y181C, K101Q/H221Y, and K101Q), the V179D series (V179D/Y181C/H221Y, V179D/Y181C, V179D/H221Y, and V179D), and the K103N series (K103N/Y181C/H221Y, K103N/Y181C, K103N/H221Y, K103N). For strains containing the mutation profiles (K101Q/Y181C, K101Q, V179D/Y181C, V179D, K103N/Y181C, and K103N), the presence of H221Y reduced NVP susceptibility by 2.1±0.5 to 3.6±0.5 fold. To the mutation profiles K101Q/H221Y, K101Q, V179D/H221Y, V179D, K103N/H221Y, and K103N, the presence of Y181C reduced NVP susceptibility by 41.9±8.4 to 1297.0±289.1 fold. For the strains containing K101Q, V179D, and K103N, the presence of Y181C/H221Y combination decreased NVP susceptibility by 100.6±32.5 to 3444.6±834.5 fold. Conclusion. On the bases of various NNRTIs mutation profiles, Y181C remarkably improved the IC50 to NVP, although H221Ymutation alone just increases 2.1 ∼ 3.6-fold resistance to NVP, the mutation could improve 100.6 ∼ 3444.6-fold resistance to NVP when it copresent with Y181C, the phenotypic drug resistance fold was improved extremely. For strains containing the mutation profiles (K101Q/Y181C, K101Q, V179D/Y181C, V179D, K103N/Y181C, and K103N), the presence of H221Y reduced NVP susceptibility by 2.1±0.5 to 3.6±0.5 fold. |
| format | Article |
| id | doaj-art-e5df820fa72d4739b1ea93e38acac25b |
| institution | Kabale University |
| issn | 2090-1240 2090-1259 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | AIDS Research and Treatment |
| spelling | doaj-art-e5df820fa72d4739b1ea93e38acac25b2025-02-03T06:05:22ZengWileyAIDS Research and Treatment2090-12402090-12592012-01-01201210.1155/2012/637263637263Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVPLiyan Jiao0Hanping Li1Lin Li2Daomin Zhuang3Yongjian Liu4Zuoyi Bao5Siyang Liu6Jingyun Li7State Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Science, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Science, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Science, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Science, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Science, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Science, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Science, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Institute of Microbiology and Epidemiology, Academy of Military Medical Science, Beijing 100071, ChinaObjective. To clarify the impact of H221Y mutation on drug resistance to NVP. Methods. 646 bp HIV-1 pol gene fragments (from 592 to 1237 nucleotide) with different NNRTIs mutation profiles from AIDS patients receiving antiretroviral therapy containing NVP regimens were introduced into pNL4-3 backbone plasmid. H221Y and (or) Y181C mutations were reverted to wild type amino acids by site-directed mutagenesis, then strains containing various mutation patterns were packaged. Phenotypic drug resistance was analyzed on TZM-bl cells. Results. 12 strains containing different drug-resistant mutation profiles were constructed, including the K101Q series (K101Q/Y181C/H221Y, K101Q/Y181C, K101Q/H221Y, and K101Q), the V179D series (V179D/Y181C/H221Y, V179D/Y181C, V179D/H221Y, and V179D), and the K103N series (K103N/Y181C/H221Y, K103N/Y181C, K103N/H221Y, K103N). For strains containing the mutation profiles (K101Q/Y181C, K101Q, V179D/Y181C, V179D, K103N/Y181C, and K103N), the presence of H221Y reduced NVP susceptibility by 2.1±0.5 to 3.6±0.5 fold. To the mutation profiles K101Q/H221Y, K101Q, V179D/H221Y, V179D, K103N/H221Y, and K103N, the presence of Y181C reduced NVP susceptibility by 41.9±8.4 to 1297.0±289.1 fold. For the strains containing K101Q, V179D, and K103N, the presence of Y181C/H221Y combination decreased NVP susceptibility by 100.6±32.5 to 3444.6±834.5 fold. Conclusion. On the bases of various NNRTIs mutation profiles, Y181C remarkably improved the IC50 to NVP, although H221Ymutation alone just increases 2.1 ∼ 3.6-fold resistance to NVP, the mutation could improve 100.6 ∼ 3444.6-fold resistance to NVP when it copresent with Y181C, the phenotypic drug resistance fold was improved extremely. For strains containing the mutation profiles (K101Q/Y181C, K101Q, V179D/Y181C, V179D, K103N/Y181C, and K103N), the presence of H221Y reduced NVP susceptibility by 2.1±0.5 to 3.6±0.5 fold.http://dx.doi.org/10.1155/2012/637263 |
| spellingShingle | Liyan Jiao Hanping Li Lin Li Daomin Zhuang Yongjian Liu Zuoyi Bao Siyang Liu Jingyun Li Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP AIDS Research and Treatment |
| title | Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP |
| title_full | Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP |
| title_fullStr | Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP |
| title_full_unstemmed | Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP |
| title_short | Impact of Novel Resistance Profiles in HIV-1 Reverse Transcriptase on Phenotypic Resistance to NVP |
| title_sort | impact of novel resistance profiles in hiv 1 reverse transcriptase on phenotypic resistance to nvp |
| url | http://dx.doi.org/10.1155/2012/637263 |
| work_keys_str_mv | AT liyanjiao impactofnovelresistanceprofilesinhiv1reversetranscriptaseonphenotypicresistancetonvp AT hanpingli impactofnovelresistanceprofilesinhiv1reversetranscriptaseonphenotypicresistancetonvp AT linli impactofnovelresistanceprofilesinhiv1reversetranscriptaseonphenotypicresistancetonvp AT daominzhuang impactofnovelresistanceprofilesinhiv1reversetranscriptaseonphenotypicresistancetonvp AT yongjianliu impactofnovelresistanceprofilesinhiv1reversetranscriptaseonphenotypicresistancetonvp AT zuoyibao impactofnovelresistanceprofilesinhiv1reversetranscriptaseonphenotypicresistancetonvp AT siyangliu impactofnovelresistanceprofilesinhiv1reversetranscriptaseonphenotypicresistancetonvp AT jingyunli impactofnovelresistanceprofilesinhiv1reversetranscriptaseonphenotypicresistancetonvp |