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

Virology. 2010 Jun 5;401(2):236-47. doi: 10.1016/j.virol.2010.02.019. Epub 2010 Mar 21.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carbohydrate Sequence
  • Cell Line
  • HIV-1 / chemistry*
  • HIV-1 / physiology*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • N-Acetylglucosaminyltransferases / deficiency
  • Polysaccharides / analysis*
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Virus Internalization*
  • Virus Replication
  • env Gene Products, Human Immunodeficiency Virus / chemistry*
  • env Gene Products, Human Immunodeficiency Virus / genetics

Substances

  • Polysaccharides
  • Recombinant Proteins
  • env Gene Products, Human Immunodeficiency Virus
  • N-Acetylglucosaminyltransferases
  • alpha-1,3-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase I