Soluble prefusion-closed HIV-envelope trimers with glycan-covered bases

• DOI: 10.1016/j.isci.2023.107403
• Publication Date: 2023-07-15T01:38:51Z
• 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. Go...; Myungjin Lee; Krisha McKee; Sandeep Narpala; Sijy O’Dell; Danealle K. Parch...; Erik-Stephane D. ...; 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
• Keywords: Envelope (radar)

Soluble HIV-1-envelope (Env) trimers elicit immune responses that target their solvent-exposed protein bases, the result of removing these from native membrane-bound context. To assess whether glycosylation could limit base responses, we introduced sequons encoding potential N-linked sites (PNGSs) into base-proximal regions. Expression and antigenic analyses indicated bearing six-introduced PNGSs to have reduced recognition. Cryo-EM analysis revealed with be prone disassembly PNGS disordered. Protein-base glycan-base induced reciprocally symmetric ELISA in which only a small fraction antibody response recognized protein-base vice versa. EM polyclonal epitope mapping –even those were stable biochemically– antibodies disassembled trimers. Introduced glycans can thus mask but introduction may yield neo-epitopes dominate response.