6xrt | pdb_00006xrt
Cryo-EM structure of SHIV-elicited RHA1.V2.01 in complex with HIV-1 Env BG505 DS-SOSIP.664
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 PubMedNeutralizing antibodies elicited by HIV-1 coevolve with viral envelope proteins (Env) in distinctive patterns, in some cases acquiring substantial breadth. We report that primary HIV-1 envelope proteins-when expressed by simian-human immunodeficiency viruses in rhesus macaques-elicited patterns of Env-antibody coevolution very similar to those in humans, including conserved immunogenetic, structural, and chemical solutions to epitope recognition and precise Env-amino acid substitutions, insertions, and deletions leading to virus persistence. The structure of one rhesus antibody, capable of neutralizing 49% of a 208-strain panel, revealed a V2 apex mode of recognition like that of human broadly neutralizing antibodies (bNAbs) PGT145 and PCT64-35S. Another rhesus antibody bound the CD4 binding site by CD4 mimicry, mirroring human bNAbs 8ANC131, CH235, and VRC01. Virus-antibody coevolution in macaques can thus recapitulate developmental features of human bNAbs, thereby guiding HIV-1 immunogen design. Recapitulation of HIV-1 Env-antibody coevolution in macaques leading to neutralization breadth.,Roark RS, Li H, Williams WB, Chug H, Mason RD, Gorman J, Wang S, Lee FH, Rando J, Bonsignori M, Hwang KK, Saunders KO, Wiehe K, Moody MA, Hraber PT, Wagh K, Giorgi EE, Russell RM, Bibollet-Ruche F, Liu W, Connell J, Smith AG, DeVoto J, Murphy AI, Smith J, Ding W, Zhao C, Chohan N, Okumura M, Rosario C, Ding Y, Lindemuth E, Bauer AM, Bar KJ, Ambrozak D, Chao CW, Chuang GY, Geng H, Lin BC, Louder MK, Nguyen R, Zhang B, Lewis MG, Raymond DD, Doria-Rose NA, Schramm CA, Douek DC, Roederer M, Kepler TB, Kelsoe G, Mascola JR, Kwong PD, Korber BT, Harrison SC, Haynes BF, Hahn BH, Shaw GM Science. 2021 Jan 8;371(6525):eabd2638. doi: 10.1126/science.abd2638. Epub 2020 , Nov 19. PMID:33214287[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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