Site-Specific Glycosylation of Virion-Derived HIV-1 Env Is Mimicked by a Soluble Trimeric Immunogen.

Autor:	Struwe WB; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12 Mansfield Road, OX1 3TA, UK., Chertova E; AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Allen JD; Biological Sciences and the Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK., Seabright GE; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Biological Sciences and the Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK., Watanabe Y; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Biological Sciences and the Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK., Harvey DJ; Biological Sciences and the Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK; Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7FZ, UK., Medina-Ramirez M; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands., Roser JD; AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Smith R; AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Westcott D; AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Keele BF; AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Bess JW Jr; AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Sanders RW; Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA; Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands., Lifson JD; AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, MD, USA., Moore JP; Department of Microbiology and Immunology, Weill Cornell Medical College, Cornell University, New York, NY, USA. Electronic address: jpm2003@med.cornell.edu., Crispin M; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Biological Sciences and the Institute for Life Sciences, University of Southampton, Southampton SO17 1BJ, UK. Electronic address: max.crispin@soton.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2018 Aug 21; Vol. 24 (8), pp. 1958-1966.e5.
DOI:	10.1016/j.celrep.2018.07.080
Abstrakt:	Many broadly neutralizing antibodies (bnAbs) against HIV-1 recognize and/or penetrate the glycan shield on native, virion-associated envelope glycoprotein (Env) spikes. The same bnAbs also bind to recombinant, soluble trimeric immunogens based on the SOSIP design. While SOSIP trimers are close structural and antigenic mimics of virion Env, the extent to which their glycan structures resemble ones on infectious viruses is undefined. Here, we compare the overall glycosylation of gp120 and gp41 subunits from BG505 (clade A) virions produced in a lymphoid cell line with those from recombinant BG505 SOSIP trimers, including CHO-derived clinical grade material. We also performed detailed site-specific analyses of gp120. Glycans relevant to key bnAb epitopes are generally similar on the recombinant SOSIP and virion-derived Env proteins, although the latter do contain hotspots of elevated glycan processing. Knowledge of native versus recombinant Env glycosylation will guide vaccine design and manufacturing programs. (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu