{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T15:55:48Z","timestamp":1762444548471},"reference-count":52,"publisher":"American Society for Microbiology","issue":"14","license":[{"start":{"date-parts":[[2015,7,15]],"date-time":"2015-07-15T00:00:00Z","timestamp":1436918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2015,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>The effect of antiretroviral drug resistance mutations on cytotoxic T lymphocyte (CTL) recognition has been analyzed in HIV-1 subtype B infections, but it remains unclear in infections by other HIV-1 subtypes that are epidemic in countries where antiretroviral drugs are not effectively used. We investigated the effect of nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI)-resistance mutations (Y181C, Y181I, and Y181V) on epitope recognition by CTLs specific for 3 different HIV-1 epitopes (HLA-A*02:01-restricted IV10, HLA-B*35:01-restricted NY9, and HLA-C*12:02-restricted KY9) in subtype B and subtype A\/E infections and the accumulation of these mutations in treatment-naive Japanese and Vietnamese. These NNRTI-resistance mutations critically affected NY9-specific and KY9-specific T cell responses in the subtype B infections, whereas they showed a different effect on IV10-specific T cell responses among the subtype B-infected individuals. These mutations affected IV10-specific T cell responses but weakly affected NY9-specific T cell responses in the subtype A\/E infections. The substitution at position 3 of NY9 epitope which was found in the subtype A\/E virus differently influenced the peptide binding to HLA-B*35:01, suggesting that the differences in peptide binding may result in the differences in T cell recognition between the subtype B virus and A\/E virus infections. The Y181C mutation was found to be accumulating in treatment-naive Vietnamese infected with the subtype A\/E virus. The present study demonstrated different effects of NNRTI-resistance RT181 mutations on CTL responses between the 2 subtype infections. The Y181C mutation may influence HIV-1 control by the CTLs in Vietnam, since this mutation has been accumulating in treatment-naive Vietnamese.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Antiretroviral therapy leads to the emergence of drug-resistant HIV-1, resulting in virological and clinical failures. Though HIV-1-specific CTLs play a critical role in HIV-1 infection, some of drug resistance mutations located in CTL epitopes are known to affect HIV-1-specific CTL responses. Nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistance RT181 mutations are frequently observed in patients treated with NNRTIs. Such drug resistance mutations may have an influence on immune control by HIV-1-specific CTLs, especially in countries where antiretroviral drugs are not effectively used. We here investigated the effect of three NNRTI-resistance RT181 mutations on immune responses by HIV-1-specific CTLs and the recent accumulation of these mutations in treatment-naive Vietnamese infected with HIV-1 subtype A\/E virus. RT181 mutations affected CTL recognition in both subtype A\/E and B infections, while the RT Y181C mutation has been accumulating in treatment-naive Vietnamese. The results suggest that the Y181C mutation may influence HIV-1 control by CTLs in Vietnam.<\/jats:p>","DOI":"10.1128\/jvi.00974-15","type":"journal-article","created":{"date-parts":[[2015,5,14]],"date-time":"2015-05-14T02:21:41Z","timestamp":1431570101000},"page":"7363-7372","update-policy":"http:\/\/dx.doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Different Effects of Nonnucleoside Reverse Transcriptase Inhibitor Resistance Mutations on Cytotoxic T Lymphocyte Recognition between HIV-1 Subtype B and Subtype A\/E Infections"],"prefix":"10.1128","volume":"89","author":[{"given":"Nozomi","family":"Kuse","sequence":"first","affiliation":[{"name":"Center for AIDS Research, Kumamoto University, Kumamoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Arif","family":"Rahman","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Kumamoto University, Kumamoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hayato","family":"Murakoshi","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Kumamoto University, Kumamoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giang Van","family":"Tran","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Kumamoto University, Kumamoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takayuki","family":"Chikata","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Kumamoto University, Kumamoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madoka","family":"Koyanagi","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Kumamoto University, Kumamoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kinh Van","family":"Nguyen","sequence":"additional","affiliation":[{"name":"National Hospital of Tropical Diseases, Dong Da District, Hanoi, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroyuki","family":"Gatanaga","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Kumamoto University, Kumamoto, Japan"},{"name":"AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichi","family":"Oka","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Kumamoto University, Kumamoto, Japan"},{"name":"AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masafumi","family":"Takiguchi","sequence":"additional","affiliation":[{"name":"Center for AIDS Research, Kumamoto University, Kumamoto, Japan"},{"name":"International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.9.6103-6110.1994"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.68.7.4650-4655.1994"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5359.2103"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2357"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0297-212"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.78.16.8927-8930.2004"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00171-10"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.3.375"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.19.9306-9312.2000"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.11.7212"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAI.0b013e3181fe946e"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2014.03.003"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-011-0222-1"},{"key":"e_1_3_3_15_2","volume-title":"HIV-1 drug resistance mutations (DRMs) for point of care (POC) testing","author":"Stanford University","year":"2014","unstructured":"Stanford University. 24 November 2014, posting date. 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