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The formation of a correctly folded and natively glycosylated HIV-1 viral spike is dependent on protease cleavage of the gp160 precursor protein in the Golgi apparatus. Cleavage induces a compact structure, which not only renders the spike capable of fusion but also limits further maturation of its extensive glycosylation. The redirection of the glycosylation pathway to preserve underprocessed oligomannose-type glycans is an important feature in immunogen design as glycans contribute to or influence the epitopes of numerous broadly neutralizing antibodies. Here, we compare quantitative site-specific analysis of a recombinant, trimeric mimic of the native HIV-1 viral spike (BG505 SOSIP.664) to the corresponding uncleaved pseudotrimer and the matched gp120 monomer. We present a detailed molecular map of trimer-associated glycan remodelling which forms a localised subdomain of the native mannose patch. The formation of native trimers is a critical design feature in shaping the glycan epitopes presented on recombinant vaccine candidates. IMPORTANCE: The envelope spike of the human immunodeficiency virus (HIV-1) is a target for antibody-based neutralization. In some patients infected with HIV-1, highly potent antibodies have been isolated that can neutralize a wide range of circulating viruses. It is a goal of HIV-1 vaccine research to elicit these antibodies by immunization with recombinant mimics of the viral spike. These antibodies have evolved to recognize the dense array of glycans that coat the surface of the viral molecule. We show how the structure of these glycans are shaped by steric constraints imposed upon them by the native folding of the viral spike. This information is important in guiding the development of vaccine candidates.

Original publication

DOI

10.1128/JVI.01894-16

Type

Journal article

Journal

Journal of Virology

Publisher

American Society for Microbiology

Publication Date

15/01/2017