IFITM Proteins Restrict HIV-1 Infection by Antagonizing the Envelope Glycoprotein

Cell Rep. 2015 Oct 6;13(1):145-156. doi: 10.1016/j.celrep.2015.08.055. Epub 2015 Sep 17.

Abstract

The interferon-induced transmembrane (IFITM) proteins have been recently shown to restrict HIV-1 and other viruses. Here, we provide evidence that IFITM proteins, particularly IFITM2 and IFITM3, specifically antagonize the HIV-1 envelope glycoprotein (Env), thereby inhibiting viral infection. IFITM proteins interact with HIV-1 Env in viral producer cells, leading to impaired Env processing and virion incorporation. Notably, the level of IFITM incorporation into HIV-1 virions does not strictly correlate with the extent of inhibition. Prolonged passage of HIV-1 in IFITM-expressing T lymphocytes leads to emergence of Env mutants that overcome IFITM restriction. The ability of IFITMs to inhibit cell-to-cell infection can be extended to HIV-1 primary isolates, HIV-2 and SIVs; however, the extent of inhibition appears to be virus-strain dependent. Overall, our study uncovers a mechanism by which IFITM proteins specifically antagonize HIV-1 Env to restrict HIV-1 infection and provides insight into the specialized role of IFITMs in HIV infection.

Publication types

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

MeSH terms

  • Cell Communication
  • Gene Expression Regulation
  • HEK293 Cells
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / metabolism
  • HIV Envelope Protein gp160 / genetics*
  • HIV Envelope Protein gp160 / metabolism
  • HIV Envelope Protein gp41 / genetics
  • HIV Envelope Protein gp41 / metabolism
  • HIV-1 / genetics*
  • HIV-1 / metabolism
  • HIV-2 / genetics
  • HIV-2 / metabolism
  • HeLa Cells
  • Host-Pathogen Interactions
  • Humans
  • Jurkat Cells
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / virology
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Primary Cell Culture
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / immunology*
  • Signal Transduction
  • Simian Immunodeficiency Virus / genetics
  • Simian Immunodeficiency Virus / metabolism
  • Virion / genetics
  • Virion / metabolism
  • Virus Internalization

Substances

  • HIV Envelope Protein gp120
  • HIV Envelope Protein gp160
  • HIV Envelope Protein gp41
  • IFITM2 protein, human
  • IFITM3 protein, human
  • Membrane Proteins
  • RNA-Binding Proteins