title: IFITM-Family Proteins: The Cell's First Line of Antiviral Defense.
abstract: Animal cells use a wide variety of mechanisms to slow or prevent replication of viruses. These mechanisms are usually mediated by antiviral proteins whose expression and activities can be constitutive but are frequently amplified by interferon induction. Among these interferon-stimulated proteins, members of the IFITM (interferon-induced transmembrane) family are unique because they prevent infection before a virus can traverse the lipid bilayer of the cell. At least three human IFITM proteins-IFITM1, IFITM2, and IFITM3-have antiviral activities. These activities limit infection in cultured cells by many viruses, including dengue virus, Ebola virus, influenza A virus, severe acute respiratory syndrome coronavirus, and West Nile virus. Murine Ifitm3 controls influenza A virus infection in vivo, and polymorphisms in humanIFITM3correlate with the severity of both seasonal and highly pathogenic avian influenza virus. Here we review the discovery and characterization of the IFITM proteins, describe the spectrum of their antiviral activities, and discuss potential mechanisms underlying these effects.
authors.affiliation: Department of Infectious Diseases, The Scripps Research Institute, Jupiter, Florida 33458.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Bailey
authors.affiliation: Department of Infectious Diseases, The Scripps Research Institute, Jupiter, Florida 33458.
authors.forename: Guocai
authors.initials: G
authors.lastname: Zhong
authors.affiliation: Department of Cell Biology and Neuroscience, College of Natural and Agricultural Sciences, University of California, Riverside, California 92521.
authors.forename: I-Chueh
authors.initials: IC
authors.lastname: Huang
authors.affiliation: Department of Infectious Diseases, The Scripps Research Institute, Jupiter, Florida 33458.
authors.forename: Michael
authors.initials: M
authors.lastname: Farzan
keywords: Ebola virus; IFITM3; SARS coronavirus; dengue virus; flavivirus; influenza A virus; interferon; restriction factor; viral entry