Mutation of Glycosylation Sites in BST-2 Leads to Its Accumulation at Intracellular CD63-Positive Vesicles without Affecting Its Antiviral Activity against Multivesicular Body-Targeted HIV-1 and Hepatitis B Virus

Viruses. 2016 Feb 29;8(3):62. doi: 10.3390/v8030062.

Abstract

BST-2/tetherin blocks the release of various enveloped viruses including HIV-1 with a "physical tethering" model. The detailed contribution of N-linked glycosylation to this model is controversial. Here, we confirmed that mutation of glycosylation sites exerted an effect of post-translational mis-trafficking, leading to an accumulation of BST-2 at intracellular CD63-positive vesicles. BST-2 with this phenotype potently inhibited the release of multivesicular body-targeted HIV-1 and hepatitis B virus, without affecting the co-localization of BST-2 with EEA1 and LAMP1. These results suggest that N-linked glycosylation of human BST-2 is dispensable for intracellular virion retention and imply that this recently discovered intracellular tethering function may be evolutionarily distinguished from the canonical antiviral function of BST-2 by tethering nascent virions at the cell surface.

Keywords: BST-2; HBV; HIV-1; glycosylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism*
  • Cell Line
  • Epithelial Cells / immunology
  • Epithelial Cells / virology
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Glycosylation
  • HIV-1 / immunology*
  • Hepatitis B virus / immunology*
  • Hepatocytes / immunology
  • Hepatocytes / virology
  • Humans
  • Multivesicular Bodies / chemistry
  • Multivesicular Bodies / immunology*
  • Multivesicular Bodies / virology*
  • Mutant Proteins / genetics
  • Mutant Proteins / metabolism*
  • Mutation*
  • Tetraspanin 30 / analysis

Substances

  • Antigens, CD
  • BST2 protein, human
  • CD63 protein, human
  • GPI-Linked Proteins
  • Mutant Proteins
  • Tetraspanin 30