Characteristics of IFITM, the Newly Identified IFN-inducible anti-HIV-1 Family Proteins

Microbes Infect. 2013 Apr;15(4):280-90. doi: 10.1016/j.micinf.2012.12.003. Epub 2013 Jan 30.

Abstract

IFN-inducible IFITM proteins (IFITM1, 2, and 3) inhibit the replication of various viruses including HIV-1 through poorly understood mechanisms. Here, we further analyzed characteristics of these newly identified HIV-1 restriction factors. Firstly, in contrast to other anti-HIV-1 proteins, such as tetherin and APOBEC3G, IFITMs were resistant to a down-regulation of surface expression or degradation by HIV-1 proteins. Secondly, the enforced expression of IFITMs reduced the production of HIV-1 viruses from cells transfected with proviral plasmids containing whole viral sequences. Although their inhibitory activities were modest when compared to that of tetherin, IFITMs, but not tetherin, directly reduced the expression of HIV-1 proteins including Gag, Vif and Nef. Of importance, however, IFITMs had no inhibitory effect when these viral proteins were expressed by codon-optimized cDNAs that bypassed the viral-specific expression machinery. Indeed, our results supported the idea that IFITMs interfere with viral protein expression mediated by double-stranded viral RNAs, such as RRE and TAR. Finally, the S-palmitoylation of IFITMs, which is crucial for their anti-influenza virus activity, was not required for their anti-HIV-1 activity, indicating that IFITMs restrict these viruses at different steps. These characteristics lead to a better understanding of the mechanism by which IFITMs restrict HIV-1 and other viruses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Differentiation / immunology*
  • Cell Line
  • HIV-1 / immunology*
  • HIV-1 / physiology*
  • Humans
  • Membrane Proteins / immunology*
  • RNA-Binding Proteins / immunology*
  • Virus Replication*
  • gag Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors
  • nef Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors
  • vif Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors

Substances

  • Antigens, Differentiation
  • IFITM2 protein, human
  • IFITM3 protein, human
  • Membrane Proteins
  • RNA-Binding Proteins
  • gag Gene Products, Human Immunodeficiency Virus
  • leu-13 antigen
  • nef Gene Products, Human Immunodeficiency Virus
  • nef protein, Human immunodeficiency virus 1
  • vif Gene Products, Human Immunodeficiency Virus
  • vif protein, Human immunodeficiency virus 1