title: IFITM Proteins Restrict HIV-1 Infection by Antagonizing the Envelope Glycoprotein.
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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Jingyou
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Minghua
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Jordan
authors.initials: J
authors.lastname: Wilkins
authors.affiliation: McGill AIDS Centre, Lady Davis Institute, Montreal, QC H3T 1E2, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.
authors.forename: Shilei
authors.initials: S
authors.lastname: Ding
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Talia H
authors.initials: TH
authors.lastname: Swartz
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Esposito
authors.affiliation: Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA.
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Zheng
authors.affiliation: Virus-Cell Interaction Section, HIV Dynamics and Replication Program, National Cancer Institute-Frederick, Frederick, MD 21702, USA.
authors.forename: Eric O
authors.initials: EO
authors.lastname: Freed
authors.affiliation: McGill AIDS Centre, Lady Davis Institute, Montreal, QC H3T 1E2, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.
authors.forename: Chen
authors.initials: C
authors.lastname: Liang
authors.affiliation: Division of Infectious Diseases, Department of Medicine, Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029, USA.
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Chen
authors.affiliation: Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, MO 65211, USA. Electronic address: liushan@missouri.edu.
authors.forename: Shan-Lu
authors.initials: SL
authors.lastname: Liu
mesh_terms: D002450:Cell Communication; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism; D019302:HIV Envelope Protein gp160 / Q000235:genetics* / Q000378:metabolism; D015700:HIV Envelope Protein gp41 / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D015498:HIV-2 / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D019169:Jurkat Cells; D007963:Leukocytes, Mononuclear / Q000276:immunology* / Q000821:virology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D061251:Primary Cell Culture; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism; D014771:Virion / Q000235:genetics / Q000378:metabolism; D053586:Virus Internalization
chemical_list: D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; C080081:IFITM2 protein, human; C080082:IFITM3 protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins