44
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The Glycan Shield of HIV Is Predominantly Oligomannose Independently of Production System or Viral Clade

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The N-linked oligomannose glycans of HIV gp120 are a target for both microbicide and vaccine design. The extent of cross-clade conservation of HIV oligomannose glycans is therefore a critical consideration for the development of HIV prophylaxes. We measured the oligomannose content of virion-associated gp120 from primary virus from PBMCs for a range of viral isolates and showed cross-clade elevation (62–79%) of these glycans relative to recombinant, monomeric gp120 (∼30%). We also confirmed that pseudoviral production systems can give rise to notably elevated gp120 oligomannose levels (∼98%), compared to gp120 derived from a single-plasmid viral system using the HIV LAI backbone (56%). This study highlights differences in glycosylation between virion-associated and recombinant gp120.

          Related collections

          Most cited references41

          • Record: found
          • Abstract: not found
          • Article: not found

          Assembly of asparagine-linked oligosaccharides.

            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            HIV vaccine design and the neutralizing antibody problem.

              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Antibody domain exchange is an immunological solution to carbohydrate cluster recognition.

              Human antibody 2G12 neutralizes a broad range of human immunodeficiency virus type 1 (HIV-1) isolates by binding an unusually dense cluster of carbohydrate moieties on the "silent" face of the gp120 envelope glycoprotein. Crystal structures of Fab 2G12 and its complexes with the disaccharide Manalpha1-2Man and with the oligosaccharide Man9GlcNAc2 revealed that two Fabs assemble into an interlocked VH domain-swapped dimer. Further biochemical, biophysical, and mutagenesis data strongly support a Fab-dimerized antibody as the prevalent form that recognizes gp120. The extraordinary configuration of this antibody provides an extended surface, with newly described binding sites, for multivalent interaction with a conserved cluster of oligomannose type sugars on the surface of gp120. The unique interdigitation of Fab domains within an antibody uncovers a previously unappreciated mechanism for high-affinity recognition of carbohydrate or other repeating epitopes on cell or microbial surfaces.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2011
                16 August 2011
                : 6
                : 8
                : e23521
                Affiliations
                [1 ]Department of Biochemistry, Oxford Glycobiology Institute, University of Oxford, Oxford, United Kingdom
                [2 ]Department of Immunology and Microbial Science and IAVI Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, United States of America
                [3 ]Ragon Institute of MGH, MIT and Harvard, Boston, Massachusetts, United States of America
                University of California , San Francisco, United States of America
                Author notes

                Conceived and designed the experiments: CB KJD RAD DRB MC CNS. Performed the experiments: CB KJD DCD VT. Analyzed the data: CB KJD DCD RAD DRB MC CNS. Wrote the paper: CB KJD DRB MC CNS.

                Article
                PONE-D-11-09577
                10.1371/journal.pone.0023521
                3156772
                21858152
                d6e682e8-d5eb-43f7-8cf3-ed4b609ebdc5
                Bonomelli et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 26 May 2011
                : 19 July 2011
                Page count
                Pages: 7
                Categories
                Research Article
                Biology
                Biochemistry
                Glycobiology
                Carbohydrates
                Glycoproteins
                Proteins
                Immune System Proteins
                Protein Structure
                Immunology
                Immunity
                Adaptive Immunity
                Immune Activation
                Immunity to Infections
                Immune Response
                Immune System
                Immunoglobulins
                Microbiology
                Virology
                Viral Structure
                Subviral Particles
                Viral Envelope
                Viral Transmission and Infection
                Viral Attachment
                Viral Entry
                Antivirals
                Immunodeficiency Viruses
                Viral Immune Evasion
                Viral Replication
                Viral Vaccines
                Viruslike Particles
                Immunity
                Medicine
                Infectious Diseases
                Viral Diseases
                HIV
                Retrovirology and HIV immunopathogenesis

                Uncategorized
                Uncategorized

                Comments

                Comment on this article