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.

Cited by papers we hold 5

• IFITM proteins: Understanding their diverse roles in viral infection, cancer, and immunity · 2023
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• Neutralizing antibody responses elicited by SARS-CoV-2 mRNA vaccination wane over time and are boosted by breakthrough infection · 2022
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• IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro · 2021
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• IFITM Genes, Variants, and Their Roles in the Control and Pathogenesis of Viral Infections · 2019
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• Resistance of Transmitted Founder HIV-1 to IFITM-Mediated Restriction · 2016
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