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

Jingyou Yu, Minghua Li, Jordan Wilkins, Shilei Ding, Talia H. Swartz, Anthony M. Esposito, Yi Min Zheng, Eric O. Freed, Chen Liang, Benjamin K. Chen, Shan Lu Liu

Research output: Contribution to journalArticlepeer-review

119 Scopus citations

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.

Original languageEnglish
Pages (from-to)145-156
Number of pages12
JournalCell Reports
Volume13
Issue number1
DOIs
StatePublished - 6 Oct 2015

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