ArticlePathogens (Basel, Switzerland)2025
Multiple Mechanisms of HIV-1 Resistance to PGT135 in a Chinese Subtype B' Slow Progressor.
Yuanyuan Hu, Shasha Sun, Ying Liu, Li Ren, Xintao Hu, Yuhua Ruan, Liying Ma, Hao Liang, Yiming Shao, Kunxue Hong and 2 more
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In one paragraphArticle in Pathogens (Basel, Switzerland), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 · Who and what moneyAuthors and funding
12 authors.
Yuanyuan HuGuangxi Key Laboratory of AIDS Prevention and Treatment & Biosafety III Laboratory, Guangxi Medical University, Nanning 530021, China.
Shasha SunNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Ying LiuNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.ORCID 0000-0002-9391-9707 Li RenNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Xintao HuNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.ORCID 0000-0002-6552-9357 Yuhua RuanNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Liying MaNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Hao LiangGuangxi Key Laboratory of AIDS Prevention and Treatment & Biosafety III Laboratory, Guangxi Medical University, Nanning 530021, China.ORCID 0000-0001-7534-5124 Yiming ShaoNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.ORCID 0000-0002-9416-190X Kunxue HongNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Sen ZouNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.
Yanling HaoNational Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 102206, China.ORCID 0009-0009-9317-650X Funding
International Cooperation Grant from the Ministry of Science and Technology of China 2016YFE0107600National Key Research and Development Program of China 2024YFC2309501National Natural Science Foundation of China 82301185SKLID key project 2019SKLID602
6 · The paper itselfAbstract
We investigated HIV-1 immune evasion mechanisms in a slow progressor (CBJC515) by constructing pseudoviruses expressing autologous Env proteins. Intriguingly, all pseudoviruses exhibited resistance to the broadly neutralizing antibody (bNAb) PGT135. Using site-directed mutagenesis and chimeric Env construction, we identified distinct escape mechanisms: early 2005 strains lost the N332 glycan site, while 2006/2008 strains retained key epitopes but developed resistance through structural modifications in the V1/V4/C2 regions or acquired novel N-glycosylation sites (N398/N611). These findings provide insights into how HIV-1 can escape from N332-directed bNAb responses without altering the epitope itself. Furthermore, chimeric experiments also elucidated regional co-evolution and functional maintenance: the V1V2 region broadly interfered with envelope protein function, while the V3 region may exhibit compensatory activity, restoring functionality and mitigating deleterious polymorphisms in other regions to keep Env antigenic diversity. These results offer valuable mechanistic clues that may inform the development of next-generation HIV-1 vaccines.
Indexed as
env Gene Products, Human Immunodeficiency VirusHIV-1HIV AntibodiesHIV InfectionsImmune EvasionAntibodies, NeutralizingEast Asian PeopleEpitopesHumansAntibodies, Neutralizingenv Gene Products, Human Immunodeficiency VirusEpitopesHIV AntibodiesbNAbHIV-1neutralization resistancepseudovirusslow progressorV3-glycan
Identifiers
PMID40559564
PMCPMC12196039
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