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TitleAnti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller.
Journal, issue, pagesCell Host Microbe, Vol. 31, Issue 8, Page 1275-11287.e8, Year 2023
Publish dateAug 9, 2023
AuthorsLuis M Molinos-Albert / Eduard Baquero / Mélanie Bouvin-Pley / Valérie Lorin / Caroline Charre / Cyril Planchais / Jordan D Dimitrov / Valérie Monceaux / Matthijn Vos / / Laurent Hocqueloux / Jean-Luc Berger / Michael S Seaman / Martine Braibant / Véronique Avettand-Fenoël / Asier Sáez-Cirión / Hugo Mouquet /
PubMed AbstractHIV-1 broadly neutralizing antibodies (bNAbs) can decrease viremia but are usually unable to counteract autologous viruses escaping the antibody pressure. Nonetheless, bNAbs may contribute to natural ...HIV-1 broadly neutralizing antibodies (bNAbs) can decrease viremia but are usually unable to counteract autologous viruses escaping the antibody pressure. Nonetheless, bNAbs may contribute to natural HIV-1 control in individuals off antiretroviral therapy (ART). Here, we describe a bNAb B cell lineage elicited in a post-treatment controller (PTC) that exhibits broad seroneutralization and show that a representative antibody from this lineage, EPTC112, targets a quaternary epitope in the glycan-V3 loop supersite of the HIV-1 envelope glycoprotein. The cryo-EM structure of EPTC112 complexed with soluble BG505 SOSIP.664 envelope trimers revealed interactions with N301- and N156-branched N-glycans and the GDIR V3 loop motif. Although the sole contemporaneous virus circulating in this PTC was resistant to EPTC112, it was potently neutralized by autologous plasma IgG antibodies. Our findings illuminate how cross-neutralizing antibodies can alter the HIV-1 infection course in PTCs and may control viremia off-ART, supporting their role in functional HIV-1 cure strategies.
External linksCell Host Microbe / PubMed:37433296
MethodsEM (single particle)
Resolution3.2 Å
Structure data

16493

8c8t

EMDB-16493, PDB-8c8t:
cryo-EM structure of BG505 SOSIP.664 HIV-1 Env trimer in complex with bNAbs EPTC112 and 3BNC117
Method: EM (single particle) / Resolution: 3.2 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • homo sapiens (human)
  • human immunodeficiency virus 1
KeywordsIMMUNE SYSTEM / HIV / post-treatment controller / broadly neutralizing antibodies / V3-site

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