2015
DOI: 10.1128/jvi.00628-15
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Comparative Analysis of the Glycosylation Profiles of Membrane-Anchored HIV-1 Envelope Glycoprotein Trimers and Soluble gp140

Abstract: A vaccine that protects against human immunodeficiency virus type 1 (HIV-1) infection should elicit antibodies that bind to the surface envelope glycoproteins on the membrane of the virus. The envelope glycoproteins have an extensive coat of carbohydrates (glycans), some of which are recognized by virus-neutralizing antibodies and some of which protect the virus from neutralizing antibodies. We found that the HIV-1 membrane envelope glycoproteins have a unique pattern of carbohydrates, with many high-mannose g… Show more

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Cited by 100 publications
(137 citation statements)
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“…Raising antibodies against such proteins may therefore benefit from the application of new, recently described methods (78). The glycan composition analysis further reinforces how the uncleaved gp140s lack the steric constraints imposed when the gp120 subunits are components of properly assembled trimers; accordingly, the gp140 UNC -Fd-His glycans are much more highly processed than those on the native-like SOSIP.664-His trimers (39,79). Finally, the uncleaved CZA97.012 gp140 proteins contain a substantial proportion of gp120 subunits with scrambled disulfide bonds, particularly in the V1V2 region; the aberrant subunits further contribute to the nonnative antigenicity and associated aberrant structural and aggregation properties of these proteins.…”
Section: Discussionmentioning
confidence: 93%
“…Raising antibodies against such proteins may therefore benefit from the application of new, recently described methods (78). The glycan composition analysis further reinforces how the uncleaved gp140s lack the steric constraints imposed when the gp120 subunits are components of properly assembled trimers; accordingly, the gp140 UNC -Fd-His glycans are much more highly processed than those on the native-like SOSIP.664-His trimers (39,79). Finally, the uncleaved CZA97.012 gp140 proteins contain a substantial proportion of gp120 subunits with scrambled disulfide bonds, particularly in the V1V2 region; the aberrant subunits further contribute to the nonnative antigenicity and associated aberrant structural and aggregation properties of these proteins.…”
Section: Discussionmentioning
confidence: 93%
“…Three of the trimer data sets are available in the literature, originally generated by the Desaire laboratory (25), the Crispin laboratory (46), and the Dell laboratory (48). Eight additional Env trimers were characterized for the present report.…”
Section: Resultsmentioning
confidence: 99%
“…A subsequent attempt to analyze the glycans at each site on virion-derived Env yielded an incomplete data set-only 13 glycopeptides were identified in total, and most of the glycan sites were not detected (45). More recently, Go et al published a site-by-site glycosylation analysis of a recombinant JR-FL (clade B) Env trimer which yielded information on every site and identified Ͼ600 different glycoforms, a 30-fold increase over the earlier study on virion Env (25). The recombinant JR-FL trimer used in that study, a membrane-anchored gp150 protein purified by nickel-nitrilotriacetic acid (Ni-NTA) affinity, had multiple high-mannose glycans at specific sites, consistent with the original glycan-based virion analyses (43,44).…”
mentioning
confidence: 99%
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