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TitleStructural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies.
Journal, issue, pagesJ Exp Med, Vol. 222, Issue 10, Year 2025
Publish dateOct 6, 2025
AuthorsRyan S Roark / Rumi Habib / Jason Gorman / Hui Li / Andrew Jesse Connell / Mattia Bonsignori / Yicheng Guo / Michael P Hogarty / Adam S Olia / Kirsten J Sowers / Baoshan Zhang / Frederic Bibollet-Ruche / Tatsiana Bylund / Sean Callaghan / John W Carey / Gabriele Cerutti / Darcy R Harris / Wanting He / Emily Lewis / Tracy Liu / Rosemarie D Mason / Yujie Qiao / Younghoon Park / Juliette M Rando / Ajay Singh / Jeremy J Wolff / Q Paula Lei / Mark K Louder / Raiees Andrabi / Nicole A Doria-Rose / Kevin O Saunders / Michael S Seaman / Barton F Haynes / Daniel W Kulp / John R Mascola / Mario Roederer / Theodore C Pierson / Zizhang Sheng / Beatrice H Hahn / George M Shaw / Peter D Kwong / Lawrence Shapiro /
PubMed AbstractBroadly 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 ...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.
External linksJ Exp Med / PubMed:40824240 / PubMed Central
MethodsEM (single particle)
Resolution2.96 - 4.22 Å
Structure data

44728

9bnk

EMDB-44728, PDB-9bnk:
Cryo-EM structure of rhesus antibody V031-a.01 in complex with HIV-1 Env BG505 DS-SOSIP
Method: EM (single particle) / Resolution: 3.1 Å

44729

9bnl

EMDB-44729, PDB-9bnl:
Cryo-EM structure of rhesus antibody 6070-a.01 in complex with HIV-1 Env trimer Q23.17 MD39
Method: EM (single particle) / Resolution: 3.6 Å

44730

9bnm

EMDB-44730, PDB-9bnm:
Cryo-EM structure of rhesus antibody 44715-a.01 in complex with HIV-1 Env BG505 DS-SOSIP
Method: EM (single particle) / Resolution: 3.97 Å

44733

9bnp

EMDB-44733, PDB-9bnp:
Cryo-EM structure of rhesus antibody V033-a.01 in complex with HIV-1 Env BG505 DS-SOSIP
Method: EM (single particle) / Resolution: 3.17 Å

44890

9bth

EMDB-44890, PDB-9bth:
Rhesus Fab 42056-a.01 in complex with CAP256SU.wk34 RnS SOSIP Env
Method: EM (single particle) / Resolution: 4.2 Å

44891

9bti

EMDB-44891, PDB-9bti:
Rhesus Fab 40591-a.01 in complex with T250.4 RnS SOSIP Env
Method: EM (single particle) / Resolution: 4.14 Å

44892

9btj

EMDB-44892, PDB-9btj:
Rhesus Fab 6561-a.01 in complex with HIV-1 Ce1176.A3 RnS SOSIP Env
Method: EM (single particle) / Resolution: 4.22 Å

44893

9btl

EMDB-44893, PDB-9btl:
Cryo-EM structure of rhesus antibody 41328-a.01 in complex with HIV-1 Env BG505 DS-SOSIP
Method: EM (single particle) / Resolution: 2.96 Å

44897

9btv

EMDB-44897, PDB-9btv:
Cryo-EM structure of rhesus antibody T646-a.01 in complex with HIV-1 Env trimer Q23.17 MD39
Method: EM (single particle) / Resolution: 3.48 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • Homo sapiens (human)
  • macaca mulatta (Rhesus monkey)
  • human immunodeficiency virus 1
KeywordsVIRAL PROTEIN/IMMUNE SYSTEM / Neutralizing antibody / HIV-1 V2 apex / SHIV-elicited / Viral protein / IMMUNE SYSTEM / VIRAL PROTEIN-IMMUNE SYSTEM complex / HIV-1 / SOSIP / Vaccine / V2-Apex / multi-donor / SHIV

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