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: 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
• Journal: Cell reports (Cell Rep) Vol. 13 Issue 1 Pg. 145-156 (Oct 06 2015) ISSN: 2211-1247 [Electronic] United States
• PMID: 26387945 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• HIV Envelope Protein gp120
• HIV Envelope Protein gp160
• HIV Envelope Protein gp41
• IFITM2 protein, human
• IFITM3 protein, human
• Membrane Proteins
• RNA-Binding Proteins

Topics

• Cell Communication
• Gene Expression Regulation
• HEK293 Cells
• HIV Envelope Protein gp120 (genetics, metabolism)
• HIV Envelope Protein gp160 (genetics, metabolism)
• HIV Envelope Protein gp41 (genetics, metabolism)
• HIV-1 (genetics, metabolism)
• HIV-2 (genetics, metabolism)
• HeLa Cells
• Host-Pathogen Interactions
• Humans
• Jurkat Cells
• Leukocytes, Mononuclear (immunology, virology)
• Membrane Proteins (genetics, immunology)
• Primary Cell Culture
• RNA-Binding Proteins (genetics, immunology)
• Signal Transduction
• Simian Immunodeficiency Virus (genetics, metabolism)
• Virion (genetics, metabolism)
• Virus Internalization