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Title | Soluble prefusion-closed HIV-envelope trimers with glycan-covered bases. |
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Journal, issue, pages | iScience, Vol. 26, Issue 8, Page 107403, Year 2023 |
Publish date | Aug 18, 2023 |
Authors | Adam S Olia / Cheng Cheng / Tongqing Zhou / Andrea Biju / Darcy R Harris / Anita Changela / Hongying Duan / Vera B Ivleva / Wing-Pui Kong / Li Ou / Reda Rawi / Yaroslav Tsybovsky / David J Van Wazer / Angela R Corrigan / Christopher A Gonelli / Myungjin Lee / Krisha McKee / Sandeep Narpala / Sijy O'Dell / Danealle K Parchment / Erik-Stephane D Stancofski / Tyler Stephens / Ivy Tan / I-Ting Teng / Shuishu Wang / Qing Wei / Yongping Yang / Zhengrong Yang / Baoshan Zhang / / Jan Novak / Matthew B Renfrow / Nicole A Doria-Rose / Richard A Koup / Adrian B McDermott / Jason G Gall / Q Paula Lei / John R Mascola / Peter D Kwong / |
PubMed Abstract | Soluble HIV-1-envelope (Env) trimers elicit immune responses that target their solvent-exposed protein bases, the result of removing these trimers from their native membrane-bound context. To assess ...Soluble HIV-1-envelope (Env) trimers elicit immune responses that target their solvent-exposed protein bases, the result of removing these trimers from their native membrane-bound context. To assess whether glycosylation could limit these base responses, we introduced sequons encoding potential -linked glycosylation sites (PNGSs) into base-proximal regions. Expression and antigenic analyses indicated trimers bearing six-introduced PNGSs to have reduced base recognition. Cryo-EM analysis revealed trimers with introduced PNGSs to be prone to disassembly and introduced PNGS to be disordered. Protein-base and glycan-base trimers induced reciprocally symmetric ELISA responses, in which only a small fraction of the antibody response to glycan-base trimers recognized protein-base trimers and vice versa. EM polyclonal epitope mapping revealed glycan-base trimers -even those that were stable biochemically- to elicit antibodies that recognized disassembled trimers. Introduced glycans can thus mask the protein base but their introduction may yield neo-epitopes that dominate the immune response. |
External links | iScience / PubMed:37554450 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.1 Å |
Structure data | EMDB-28910, PDB-8f7t: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRAL PROTEIN / HIV-1 / Glycan / Env |