2. Academic Validation
  3. The C-terminal sequence of IFITM1 regulates its anti-HIV-1 activity

The C-terminal sequence of IFITM1 regulates its anti-HIV-1 activity

  • PLoS One. 2015 Mar 4;10(3):e0118794. doi: 10.1371/journal.pone.0118794.
Rui Jia 1,  Shilei Ding 2,  Qinghua Pan 3,  Shan-Lu Liu 4,  Wentao Qiao 5,  Chen Liang 2
Affiliations

Affiliations

  • 1 Key Laboratory of Molecular Microbiology and Biotechnology (Ministry of Education) and Key Laboratory of Microbial Functional Genomics (Tianjin), College of Life Sciences, Nankai University, Tianjin, 300071, China; Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, H3T 1E2, Canada.
  • 2 Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, H3T 1E2, Canada; Department of Medicine, McGill University, Montreal, Quebec, H3A 2B4, Canada.
  • 3 Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, H3T 1E2, Canada.
  • 4 Department of Molecular Microbiology & Immunology, School of Medicine, Bond Life Sciences Center, University of Missouri, Columbia, Missouri, 65211-7310, United States of America.
  • 5 Key Laboratory of Molecular Microbiology and Biotechnology (Ministry of Education) and Key Laboratory of Microbial Functional Genomics (Tianjin), College of Life Sciences, Nankai University, Tianjin, 300071, China.
PMID: 25738301 DOI: 10.1371/journal.pone.0118794
Abstract

The interferon-inducible transmembrane (IFITM) proteins inhibit a wide range of viruses. We previously reported the inhibition of human immunodeficiency virus type 1 (HIV-1) strain BH10 by human IFITM1, 2 and 3. It is unknown whether other HIV-1 strains are similarly inhibited by IFITMs and whether there exists viral countermeasure to overcome IFITM inhibition. We report here that the HIV-1 NL4-3 strain (HIV-1NL4-3) is not restricted by IFITM1 and its viral envelope glycoprotein is partly responsible for this insensitivity. However, HIV-1NL4-3 is profoundly inhibited by an IFITM1 mutant, known as Δ(117-125), which is deleted of 9 Amino acids at the C-terminus. In contrast to the wild type IFITM1, which does not affect HIV-1 entry, the Δ(117-125) mutant diminishes HIV-1NL4-3 entry by 3-fold. This inhibition correlates with the predominant localization of Δ(117-125) to the plasma membrane where HIV-1 entry occurs. In spite of strong conservation of IFITM1 among most species, mouse IFITM1 is 19 Amino acids shorter at its C-terminus as compared to human IFITM1 and, like the human IFITM1 mutant Δ(117-125), mouse IFITM1 also inhibits HIV-1 entry. This is the first report illustrating the role of viral envelope protein in overcoming IFITM1 restriction. The results also demonstrate the importance of the C-terminal region of IFITM1 in modulating the Antiviral function through controlling protein subcellular localization.

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