8c8t
cryo-EM structure of BG505 SOSIP.664 HIV-1 Env trimer in complex with bNAbs EPTC112 and 3BNC117
Structural highlights
FunctionQ2N0S5_9HIV1 The envelope glyprotein gp160 precursor down-modulates cell surface CD4 antigen by interacting with it in the endoplasmic reticulum and blocking its transport to the cell surface.[RuleBase:RU004292][SAAS:SAAS00139820] The gp120-gp41 heterodimer allows rapid transcytosis of the virus through CD4 negative cells such as simple epithelial monolayers of the intestinal, rectal and endocervical epithelial barriers. Both gp120 and gp41 specifically recognize glycosphingolipids galactosyl-ceramide (GalCer) or 3' sulfo-galactosyl-ceramide (GalS) present in the lipid rafts structures of epithelial cells. Binding to these alternative receptors allows the rapid transcytosis of the virus through the epithelial cells. This transcytotic vesicle-mediated transport of virions from the apical side to the basolateral side of the epithelial cells does not involve infection of the cells themselves.[SAAS:SAAS00140087] Publication Abstract from PubMedHIV-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 (324)GDIR(327) 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. Anti-V1/V3-glycan broadly HIV-1 neutralizing antibodies in a post-treatment controller.,Molinos-Albert LM, Baquero E, Bouvin-Pley M, Lorin V, Charre C, Planchais C, Dimitrov JD, Monceaux V, Vos M, Hocqueloux L, Berger JL, Seaman MS, Braibant M, Avettand-Fenoel V, Saez-Cirion A, Mouquet H Cell Host Microbe. 2023 Aug 9;31(8):1275-1287.e8. doi: , 10.1016/j.chom.2023.06.006. Epub 2023 Jul 10. PMID:37433296[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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