{"doi":"10.7554/elife.92379","title":"A remarkable genetic shift in a transmitted/founder virus broadens antibody responses against HIV-1","abstract":"A productive HIV-1 infection in humans is often established by transmission and propagation of a single transmitted/founder (T/F) virus, which then evolves into a complex mixture of variants during the lifetime of infection. An effective HIV-1 vaccine should elicit broad immune responses in order to block the entry of diverse T/F viruses. Currently, no such vaccine exists. An in-depth study of escape variants emerging under host immune pressure during very early stages of infection might provide insights into such a HIV-1 vaccine design. Here, in a rare longitudinal study involving HIV-1 infected individuals just days after infection in the absence of antiretroviral therapy, we discovered a remarkable genetic shift that resulted in near complete disappearance of the original T/F virus and appearance of a variant with H173Y mutation in the variable V2 domain of the HIV-1 envelope protein. This coincided with the disappearance of the first wave of strictly H173-specific antibodies and emergence of a second wave of Y173-specific antibodies with increased breadth. Structural analyses indicated conformational dynamism of the envelope protein which likely allowed selection of escape variants with a conformational switch in the V2 domain from an α-helix (H173) to a β-strand (Y173) and induction of broadly reactive antibody responses. This differential breadth due to a single mutational change was also recapitulated in a mouse model. Rationally designed combinatorial libraries containing 54 conformational variants of V2 domain around position 173 further demonstrated increased breadth of antibody responses elicited to diverse HIV-1 envelope proteins. These results offer new insights into designing broadly effective HIV-1 vaccines.","journal":"eLife","year":2024,"id":472978,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9469,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":820586,"name":"Gherman Uritskiy","orcid":"0000-0002-3332-0815","position":1,"is_corresponding":false},{"id":123457,"name":"Marthandan Mahalingam","orcid":null,"position":2,"is_corresponding":false},{"id":771401,"name":"Himanshu Batra","orcid":"0000-0002-0203-0591","position":3,"is_corresponding":false},{"id":777009,"name":"Subhash Chand","orcid":"0000-0002-2072-2743","position":4,"is_corresponding":false},{"id":343906,"name":"Hung V. Trinh","orcid":"0000-0001-8014-9291","position":5,"is_corresponding":false},{"id":392402,"name":"Charles Beck","orcid":"0000-0002-0967-5333","position":6,"is_corresponding":false},{"id":316935,"name":"Woong‐Hee Shin","orcid":"0000-0003-3462-0243","position":7,"is_corresponding":false},{"id":821003,"name":"Wadad AlSalmi","orcid":null,"position":8,"is_corresponding":false},{"id":593573,"name":"Gustavo H. Kijak","orcid":"0000-0002-2746-9533","position":9,"is_corresponding":false},{"id":347960,"name":"Leigh Anne Eller","orcid":"0000-0003-2043-1513","position":10,"is_corresponding":false},{"id":36907,"name":"Jérôme H. Kim","orcid":"0000-0003-0461-6438","position":11,"is_corresponding":false},{"id":316939,"name":"Daisuke Kihara","orcid":"0000-0003-4091-6614","position":12,"is_corresponding":false},{"id":332552,"name":"Sodsai Tovanabutra","orcid":"0000-0002-5946-4227","position":13,"is_corresponding":false},{"id":249714,"name":"Guido Ferrari","orcid":"0000-0001-7747-3349","position":14,"is_corresponding":false},{"id":288619,"name":"Merlin L. Robb","orcid":"0000-0003-3949-9649","position":15,"is_corresponding":false},{"id":332557,"name":"Mangala Rao","orcid":"0000-0001-9553-4969","position":16,"is_corresponding":false},{"id":123459,"name":"Venigalla B. Rao","orcid":"0000-0002-0777-6587","position":17,"is_corresponding":false},{"id":81413,"name":"Swati Jain","orcid":"0000-0002-8625-8218","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:06:01.000126Z","pmid":"38619110","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}