{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Roark RS"],"funding":["Vaccine Research Center","NIAID NIH HHS","NHLBI NIH HHS","Duke Consortium for HIV Vaccine Development","National Institutes of Health","Division of Intramural Research","Training Grant in HIV Pathogenesis","National Institute of Allergy and Infectious Diseases","Bill &amp; Melinda Gates Foundation","Duke Human Vaccine Institute","Penn Center for AIDS Research","Gates Foundation","NIH HHS"],"pagination":["e20250638"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12379892"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["222(10)"],"pubmed_abstract":["Broadly neutralizing antibodies targeting the V2 apex of HIV-1 envelope are desired as vaccine design templates, but few have been described. Here, we report 11 lineages of V2 apex-neutralizing antibodies from simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and determine cryo-EM structures for 9. A single V2 apex-neutralizing lineage accounted for cross-clade breadth in most macaques, and somatic hypermutation relative to breadth was generally low, exemplified by antibody V033-a.01 with <5% nucleotide mutation and 37% breadth (208-strain panel). Envelope complex structures revealed eight different antibody classes (one multi-donor) and the complete repertoire of all five possible recognition topologies, recapitulating canonical human modes of apex insertion and C-strand hydrogen bonding. Despite this diversity in recognition, all rhesus-V2 apex antibodies were derived from reading frame two of the DH3-15*01 gene. Collectively, these results define-in rhesus-the structural and genetic basis of HIV-1 V2 apex recognition and demonstrate unprecedented structural plasticity of a highly selected immunogenetic element."],"journal":["The Journal of experimental medicine"],"pubmed_title":["Structural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies."],"pmcid":["PMC12379892"],"funding_grant_id":["INV-041767","R01 AI160607","T32-AI007632","R61 AI 176583","P30 AI045008","R37 AI 150590","R61 AI 161818","UM1 AI 144371","R01 AI165080","INV-007939","R01 AI 167716","R01 AI 050529"],"pubmed_authors":["Connell AJ","Bibollet-Ruche F","Andrabi R","Roederer M","Guo Y","Liu T","Doria-Rose NA","Shaw GM","Park Y","Haynes BF","Roark RS","Hahn BH","Olia AS","Callaghan S","Harris DR","Seaman MS","Kulp DW","Zhang B","Wolff JJ","Kwong PD","Saunders KO","Rando JM","Lei QP","Li H","Hogarty MP","Sheng Z","Bylund T","Gorman J","Habib R","Singh A","Louder MK","Shapiro L","Cerutti G","Pierson TC","Qiao Y","Bonsignori M","Mascola JR","He W","Mason RD","Sowers KJ","Lewis E","Carey JW"],"additional_accession":[]},"is_claimable":false,"name":"Structural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies.","description":"Broadly neutralizing antibodies targeting the V2 apex of HIV-1 envelope are desired as vaccine design templates, but few have been described. Here, we report 11 lineages of V2 apex-neutralizing antibodies from simian-human immunodeficiency virus (SHIV)-infected rhesus macaques and determine cryo-EM structures for 9. A single V2 apex-neutralizing lineage accounted for cross-clade breadth in most macaques, and somatic hypermutation relative to breadth was generally low, exemplified by antibody V033-a.01 with <5% nucleotide mutation and 37% breadth (208-strain panel). Envelope complex structures revealed eight different antibody classes (one multi-donor) and the complete repertoire of all five possible recognition topologies, recapitulating canonical human modes of apex insertion and C-strand hydrogen bonding. Despite this diversity in recognition, all rhesus-V2 apex antibodies were derived from reading frame two of the DH3-15*01 gene. Collectively, these results define-in rhesus-the structural and genetic basis of HIV-1 V2 apex recognition and demonstrate unprecedented structural plasticity of a highly selected immunogenetic element.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-05-10T01:47:05.364Z","creation":"2026-04-08T01:25:23.245Z"},"accession":"S-EPMC12379892","cross_references":{"pubmed":["40824240"],"doi":["10.1084/jem.20250638"]}}