Lack of complex N-glycans on HIV-1 envelope glycoproteins preserves protein conformation and entry function |
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Authors: | Dirk Eggink,Manfred Wuhrer,Antu K. Dey,Kathryn B. David,André M. Deelder,William C. Olson,Cornelis H. Hokke,Rogier W. Sanders |
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Affiliation: | a Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center of the University of Amsterdam, 1105 AZ Amsterdam, The Netherlands b Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA c Department of Parasitology, Center of Infectious Diseases, Leiden University Medical Center, 2300 RC Leiden, The Netherlands d Progenics Pharmaceuticals, Inc. 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA |
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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. |
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Keywords: | HIV-1 Envelope glycoprotein Glycosylation DC-SIGN Oligomannose N-Acetylglucosaminyltransferase I |
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