NDLI: The Interferon-induced Transmembrane Proteins, IFITM1, IFITM2, and IFITM3 Inhibit Hepatitis C Virus Entry.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Mccartney, Erin M. Beard, Michael R. Helbig, Karla J. Bull, Rowena A. Eyre, Nicholas S. Lloyd, Andrew R. Narayana, Sumudu K. Eltahla, Auda
Description	Author Affiliation: Narayana SK ( From the School of Biological Sciences, and the Research Centre for Infectious Diseases, University of Adelaide, Adelaide, South Australia 5005, Australia, the Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, 5000, Australia, and.); Helbig KJ ( From the School of Biological Sciences, and the Research Centre for Infectious Diseases, University of Adelaide, Adelaide, South Australia 5005, Australia, the Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, 5000, Australia, and.); McCartney EM ( From the School of Biological Sciences, and the Research Centre for Infectious Diseases, University of Adelaide, Adelaide, South Australia 5005, Australia, the Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, 5000, Australia, and.); Eyre NS ( From the School of Biological Sciences, and the Research Centre for Infectious Diseases, University of Adelaide, Adelaide, South Australia 5005, Australia, the Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, 5000, Australia, and.); Bull RA ( the Inflammation and Infection Research Centre, School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.); Eltahla A ( the Inflammation and Infection Research Centre, School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.); Lloyd AR ( the Inflammation and Infection Research Centre, School of Medical Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.); Beard MR ( From the School of Biological Sciences, and the Research Centre for Infectious Diseases, University of Adelaide, Adelaide, South Australia 5005, Australia, the Centre for Cancer Biology, SA Pathology, Adelaide, South Australia, 5000, Australia, and michael.beard@adelaide.edu.au.)
Abstract	The interferon-induced transmembrane (IFITM) family of proteins have recently been identified as important host effector molecules of the type I interferon response against viruses. IFITM1 has been identified as a potent antiviral effector against hepatitis C virus (HCV), whereas the related family members IFITM2 and IFITM3 have been described to have antiviral effects against a broad range of RNA viruses. Here, we demonstrate that IFITM2 and IFITM3 play an integral role in the interferon response against HCV and act at the level of late entry stages of HCV infection. We have established that in hepatocytes, IFITM2 and IFITM3 localize to the late and early endosomes, respectively, as well as the lysosome. Furthermore, we have demonstrated that S-palmitoylation of all three IFITM proteins is essential for anti-HCV activity, whereas the conserved tyrosine residue in the N-terminal domain of IFITM2 and IFITM3 plays a significant role in protein localization. However, this tyrosine was found to be dispensable for anti-HCV activity, with mutation of the tyrosine resulting in an IFITM1-like phenotype with the retention of anti-HCV activity and co-localization of IFITM2 and IFITM3 with CD81. In conclusion, we propose that the IFITM proteins act in a coordinated manner to restrict HCV infection by targeting the endocytosed HCV virion for lysosomal degradation and demonstrate that the actions of the IFITM proteins are indeed virus and cell-type specific.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	43
Volume Number	290
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2015-10-23
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antigens, Differentiation Physiology Hepacivirus Membrane Fusion Membrane Proteins RNA-Binding Proteins Metabolism Cell Line, Tumor Endosomes Hepatitis C Physiopathology Hepatocytes Lipoylation Lysosomes Research Support, Non-U.S. Gov't Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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