6vo1
BG505 SOSIP.v5.2 in complex with rhesus macaque Fab RM20J
Structural highlights
FunctionQ2N0S6_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 (By similarity).[RuleBase:RU004292][SAAS:SAAS000328_004_020447] 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 (By similarity).[SAAS:SAAS000328_004_240990] Publication Abstract from PubMedThe induction of broad and potent immunity by vaccines is the key focus of research efforts aimed at protecting against HIV-1 infection. Soluble native-like HIV-1 envelope glycoproteins have shown promise as vaccine candidates as they can induce potent autologous neutralizing responses in rabbits and non-human primates. In this study, monoclonal antibodies were isolated and characterized from rhesus macaques immunized with the BG505 SOSIP.664 trimer to better understand vaccine-induced antibody responses. Our studies reveal a diverse landscape of antibodies recognizing immunodominant strain-specific epitopes and non-neutralizing neo-epitopes. Additionally, we isolated a subset of mAbs against an epitope cluster at the gp120-gp41 interface that recognize the highly conserved fusion peptide and the glycan at position 88 and have characteristics akin to several human-derived broadly neutralizing antibodies. Mapping the immunogenic landscape of near-native HIV-1 envelope trimers in non-human primates.,Cottrell CA, van Schooten J, Bowman CA, Yuan M, Oyen D, Shin M, Morpurgo R, van der Woude P, van Breemen M, Torres JL, Patel R, Gross J, Sewall LM, Copps J, Ozorowski G, Nogal B, Sok D, Rakasz EG, Labranche C, Vigdorovich V, Christley S, Carnathan DG, Sather DN, Montefiori D, Silvestri G, Burton DR, Moore JP, Wilson IA, Sanders RW, Ward AB, van Gils MJ PLoS Pathog. 2020 Aug 31;16(8):e1008753. doi: 10.1371/journal.ppat.1008753., eCollection 2020 Aug. PMID:32866207[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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