Lack of complex N-glycans on HIV-1 envelope glycoproteins preserves protein conformation and entry function.

TitleLack of complex N-glycans on HIV-1 envelope glycoproteins preserves protein conformation and entry function.
Publication TypeJournal Article
Year of Publication2010
AuthorsEggink D, Melchers M, Wuhrer M, van Montfort T, Dey AK, Naaijkens BA, David KB, Le Douce V, Deelder AM, Kang K, Olson WC, Berkhout B, Hokke CH, Moore JP, Sanders RW
JournalVirology
Volume401
Issue2
Pagination236-47
Date Published2010 Jun 5
ISSN1096-0341
KeywordsCarbohydrate Sequence, Cell Line, env Gene Products, Human Immunodeficiency Virus, HIV-1, Humans, Models, Molecular, Molecular Sequence Data, N-Acetylglucosaminyltransferases, Polysaccharides, Protein Conformation, Recombinant Proteins, Virus Internalization, Virus Replication
Abstract

The HIV-1 envelope glycoprotein complex (Env) is the focus of vaccine development aimed at eliciting humoral immunity. Env's extensive and heterogeneous N-linked glycosylation affects folding, binding to lectin receptors, antigenicity and immunogenicity. We characterized recombinant Env proteins and virus particles produced in mammalian cells that lack N-acetylglucosaminyltransferase I (GnTI), an enzyme necessary for the conversion of oligomannose N-glycans to complex N-glycans. Carbohydrate analyses revealed that trimeric Env produced in GnTI(-/-) cells contained exclusively oligomannose N-glycans, with incompletely trimmed oligomannose glycans predominating. The folding and conformation of Env proteins was little affected by the manipulation of the glycosylation. Viruses produced in GnTI(-/-) cells were infectious, indicating that the conversion to complex glycans is not necessary for Env entry function, although virus binding to the C-type lectin DC-SIGN was enhanced. Manipulating Env's N-glycosylation may be useful for structural and functional studies and for vaccine design.

DOI10.1016/j.virol.2010.02.019
Alternate JournalVirology
PubMed ID20304457
PubMed Central IDPMC3776475
Grant ListAI082362 / AI / NIAID NIH HHS / United States
AI36082 / AI / NIAID NIH HHS / United States
AI45463 / AI / NIAID NIH HHS / United States
P01 AI082362 / AI / NIAID NIH HHS / United States
R01 AI045463 / AI / NIAID NIH HHS / United States
R37 AI036082 / AI / NIAID NIH HHS / United States

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