{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T08:45:00Z","timestamp":1776761100283,"version":"3.51.2"},"reference-count":45,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":6,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI Grants-in-Aid for Scientific Research B","award":["20H03726"],"award-info":[{"award-number":["20H03726"]}]},{"name":"AIDS Research","award":["JP22fk0410053"],"award-info":[{"award-number":["JP22fk0410053"]}]},{"name":"AIDS Research","award":["JP25fk0410077"],"award-info":[{"award-number":["JP25fk0410077"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Disease progression during HIV-1 infection is proposed to correlate with the accumulation of virus variants that have evaded HIV-1-specific T cells; however, the multistep coevolution of HIV-1 with HIV-1-specific T cells has not been well investigated. Here, we analyzed the coevolution of HIV-1 with human leukocyte antigen (HLA)-C*14-restricted HIV-1-specific T cells in treatment-naive HLA-C*14+ people living with HIV-1 (PLWH). The analyses of T cells specific for NefYT9 wild-type (WT) or escape mutant epitopes and HIV-1 sequences in HLA-C*14+ PLWH suggested that NefQ125H was first selected by NefYT9 WT\u2013specific T cells, then NefQ125D was selected by NefYT9-6H-specific T cells. This coevolution was confirmed by longitudinal analysis of HLA-C*14+ PLWH. The CD4 count in NefQ125D virus\u2013infected HLA-C*14+ individuals was significantly lower than that in WT-virus\u2013infected HLA-C*14+ individuals, suggesting that accumulation of the NefQ125D mutant epitope correlates with disease progression. Our findings demonstrate that the multistep coevolution of HIV-1 with HLA-C-restricted HIV-1-specific T cells is associated with disease progression in HIV-1 infection.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgag105","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T15:44:20Z","timestamp":1775749460000},"source":"Crossref","is-referenced-by-count":0,"title":["Multistep coevolution of HIV-1 and human leukocyte antigen-C-restricted HIV-1-specific CD8+ T cells and the association with disease progression"],"prefix":"10.1093","volume":"5","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8907-1320","authenticated-orcid":false,"given":"Takayuki","family":"Chikata","sequence":"first","affiliation":[{"name":"Division of International Collaboration Research and Tokyo Laboratory, Joint Research Center for Human Retrovirus Infection, Kumamoto University , 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811 ,","place":["Japan"]},{"name":"AIDS Clinical Center, National Center for Global Health and Medicine, Japan Institute for Health Security , Tokyo 162-8655 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6604-3684","authenticated-orcid":false,"given":"Tomohiro","family":"Akahoshi","sequence":"additional","affiliation":[{"name":"Division of International Collaboration Research and Tokyo Laboratory, Joint Research Center for Human Retrovirus Infection, Kumamoto University , 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of International Collaboration Research and Tokyo Laboratory, Joint Research Center for Human Retrovirus Infection, Kumamoto University , 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0053-0274","authenticated-orcid":false,"given":"Hung The","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Division of International Collaboration Research and Tokyo Laboratory, Joint Research Center for Human Retrovirus Infection, Kumamoto University , 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinichi","family":"Oka","sequence":"additional","affiliation":[{"name":"AIDS Clinical Center, National Center for Global Health and Medicine, Japan Institute for Health Security , Tokyo 162-8655 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9191-9984","authenticated-orcid":false,"given":"Hiroyuki","family":"Gatanaga","sequence":"additional","affiliation":[{"name":"AIDS Clinical Center, National Center for Global Health and Medicine, Japan Institute for Health Security , Tokyo 162-8655 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8516-6442","authenticated-orcid":false,"given":"Masafumi","family":"Takiguchi","sequence":"additional","affiliation":[{"name":"Division of International Collaboration Research and Tokyo Laboratory, Joint Research Center for Human Retrovirus Infection, Kumamoto University , 2-2-1 Honjo, Chuo-ku, Kumamoto 860-0811 ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"2026042103512333700_pgag105-B1","doi-asserted-by":"crossref","first-page":"1890","DOI":"10.1073\/pnas.94.5.1890","article-title":"Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection","volume":"94","author":"Price","year":"1997","journal-title":"Proc Natl Acad Sci U S 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