National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health & Human Development (NIH/NICHD)
米国
引用
ジャーナル: Nat Struct Mol Biol / 年: 2022 タイトル: Cryo-EM structures of prefusion SIV envelope trimer. 著者: Jason Gorman / Chunyan Wang / Rosemarie D Mason / Alexandra F Nazzari / Hugh C Welles / Tongqing Zhou / Julian W Bess / Tatsiana Bylund / Myungjin Lee / Yaroslav Tsybovsky / Raffaello Verardi ...著者: Jason Gorman / Chunyan Wang / Rosemarie D Mason / Alexandra F Nazzari / Hugh C Welles / Tongqing Zhou / Julian W Bess / Tatsiana Bylund / Myungjin Lee / Yaroslav Tsybovsky / Raffaello Verardi / Shuishu Wang / Yongping Yang / Baoshan Zhang / Reda Rawi / Brandon F Keele / Jeffrey D Lifson / Jun Liu / Mario Roederer / Peter D Kwong / 要旨: Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. Here we report prefusion ...Simian immunodeficiency viruses (SIVs) are lentiviruses that naturally infect non-human primates of African origin and seeded cross-species transmissions of HIV-1 and HIV-2. Here we report prefusion stabilization and cryo-EM structures of soluble envelope (Env) trimers from rhesus macaque SIV (SIV) in complex with neutralizing antibodies. These structures provide residue-level definition for SIV-specific disulfide-bonded variable loops (V1 and V2), which we used to delineate variable-loop coverage of the Env trimer. The defined variable loops enabled us to investigate assembled Env-glycan shields throughout SIV, which we found to comprise both N- and O-linked glycans, the latter emanating from V1 inserts, which bound the O-link-specific lectin jacalin. We also investigated in situ SIV-Env trimers on virions, determining cryo-electron tomography structures at subnanometer resolutions for an antibody-bound complex and a ligand-free state. Collectively, these structures define the prefusion-closed structure of the SIV-Env trimer and delineate variable-loop and glycan-shielding mechanisms of immune evasion conserved throughout SIV evolution.