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

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

Author information

1
Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA.
2
McGill AIDS Centre, Lady Davis Institute, Montreal, QC H3T 1E2, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.
3
Division of Infectious Diseases, Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
4
Virus-Cell Interaction Section, HIV Dynamics and Replication Program, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
5
Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA. Electronic address: liushan@missouri.edu.

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.

PMID:
26387945
PMCID:
PMC4602366
DOI:
10.1016/j.celrep.2015.08.055
[Indexed for MEDLINE]
Free PMC Article

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