IFITM proteins: Understanding their diverse roles in viral infection, cancer, and immunity

J Biol Chem. 2023 Jan;299(1):102741. doi: 10.1016/j.jbc.2022.102741. Epub 2022 Nov 23.

Abstract

Interferon-induced transmembrane proteins (IFITMs) are broad spectrum antiviral factors that inhibit the entry of a wide range of clinically important pathogens including influenza A virus, HIV-1, and Dengue virus. IFITMs are thought to act primarily by antagonizing virus-cell membrane fusion in this regard. However, recent work on these proteins has uncovered novel post-entry viral restriction mechanisms. IFITMs are also increasingly thought to have a role regulating immune responses, including innate antiviral and inflammatory responses as well as adaptive T-cell and B-cell responses. Further, IFITMs may have pathological activities in cancer, wherein IFITM expression can be a marker of therapeutically resistant and aggressive disease courses. In this review, we summarize the respective literatures concerning these apparently diverse functions with a view to identifying common themes and potentially yielding a more unified understanding of IFITM biology.

Keywords: IFITM; IFITM1; IFITM2; IFITM3; IFITMs; antiviral factors; cancer; innate immunity; interferon; restriction factors; translation.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / metabolism
  • Antiviral Agents
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Neoplasms* / genetics
  • Virus Diseases* / genetics
  • Virus Internalization

Substances

  • Membrane Proteins
  • Antiviral Agents
  • Antigens, Differentiation