title: Characteristics of IFITM, the newly identified IFN-inducible anti-HIV-1 family proteins.
abstract: IFN-inducible IFITM proteins (IFITM1, 2, and 3) inhibit the replication of various viruses including HIV-1 through poorly understood mechanisms. Here, we further analyzed characteristics of these newly identified HIV-1 restriction factors. Firstly, in contrast to other anti-HIV-1 proteins, such as tetherin and APOBEC3G, IFITMs were resistant to a down-regulation of surface expression or degradation by HIV-1 proteins. Secondly, the enforced expression of IFITMs reduced the production of HIV-1 viruses from cells transfected with proviral plasmids containing whole viral sequences. Although their inhibitory activities were modest when compared to that of tetherin, IFITMs, but not tetherin, directly reduced the expression of HIV-1 proteins including Gag, Vif and Nef. Of importance, however, IFITMs had no inhibitory effect when these viral proteins were expressed by codon-optimized cDNAs that bypassed the viral-specific expression machinery. Indeed, our results supported the idea that IFITMs interfere with viral protein expression mediated by double-stranded viral RNAs, such as RRE and TAR. Finally, the S-palmitoylation of IFITMs, which is crucial for their anti-influenza virus activity, was not required for their anti-HIV-1 activity, indicating that IFITMs restrict these viruses at different steps. These characteristics lead to a better understanding of the mechanism by which IFITMs restrict HIV-1 and other viruses.
authors: Center for AIDS Research, Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto-city, Kumamoto 860-0811, Japan.
authors: Nopporn
authors: N
authors: Chutiwitoonchai
authors: Masateru
authors: M
authors: Hiyoshi
authors: Yuka
authors: Y
authors: Hiyoshi-Yoshidomi
authors: Michihiro
authors: M
authors: Hashimoto
authors: Kenzo
authors: K
authors: Tokunaga
authors: Shinya
authors: S
authors: Suzu
mesh_terms: D000943:Antigens, Differentiation / Q000276:immunology*; D002460:Cell Line; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000276:immunology*; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors
chemical_list: D000943:Antigens, Differentiation; C080081:IFITM2 protein, human; C080082:IFITM3 protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C062010:leu-13 antigen; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1
references: Nature. 2002 Aug 8;418(6898):646-50
references: 12167863
references: Mol Cell. 2003 Sep;12(3):591-601
references: 14527406
references: J Virol. 2011 Mar;85(5):2126-37
references: 21177806
references: J Virol. 2010 Aug;84(16):8332-41
references: 20534863
references: PLoS One. 2011;6(11):e27696
references: 22110726
references: J Cell Physiol. 2009 Nov;221(2):458-68
references: 19585521
references: J Virol. 2006 Aug;80(15):7645-57
references: 16840343
references: Nat Med. 2003 Nov;9(11):1398-403
references: 14528301
references: Biochem Biophys Res Commun. 2003 Aug 15;308(1):50-7
references: 12890478
references: PLoS Pathog. 2011 Jan 06;7(1):e1001258
references: 21253575
references: Front Microbiol. 2010 Nov 24;1:116
references: 21607084
references: Cell Host Microbe. 2008 Apr 17;3(4):245-52
references: 18342597
references: Nat Rev Immunol. 2008 Jul;8(7):559-68
references: 18575461
references: Nature. 2011 Apr 28;472(7344):481-5
references: 21478870
references: Dev Cell. 2005 Dec;9(6):745-56
references: 16326387
references: J Biol Chem. 2004 Feb 27;279(9):7792-8
references: 14672928
references: J Biol Chem. 2009 Dec 11;284(50):35060-72
references: 19837671
references: Cell Death Differ. 2010 Dec;17(12):1917-27
references: 20489731
references: PLoS Pathog. 2011 Oct;7(10):e1002337
references: 22046135
references: Curr HIV Res. 2009 Jan;7(1):101-8
references: 19149559
references: Nat Chem Biol. 2010 Aug;6(8):610-4
references: 20601941
references: Curr Opin Immunol. 2011 Feb;23(1):57-64
references: 21123041
references: J Biol Chem. 2004 Apr 9;279(15):14481-3
references: 14966139
references: Curr HIV Res. 2009 Jan;7(1):91-100
references: 19149558
references: J Virol. 2009 May;83(9):4574-90
references: 19244337
references: Blood. 2008 Jan 1;111(1):243-50
references: 17893228
references: Nature. 2008 Jan 24;451(7177):425-30
references: 18200009
references: Nature. 1991 Apr 11;350(6318):508-11
references: 2014052
references: Rev Med Virol. 2011 Jan;21(1):42-53
references: 21294215
references: Cell Host Microbe. 2007 Sep 13;2(3):193-203
references: 18005734
references: Cell. 1984 Oct;38(3):745-55
references: 6548414
references: Virology. 2004 Feb 20;319(2):163-75
references: 15015498
references: Cell Host Microbe. 2009 Mar 19;5(3):285-97
references: 19286137
references: Blood. 2005 Apr 15;105(8):3230-7
references: 15626739
references: Cell. 2009 Dec 24;139(7):1243-54
references: 20064371
references: J Virol. 2010 Dec;84(24):12646-57
references: 20943977
references: Science. 2003 Nov 7;302(5647):1056-60
references: 14564014
references: J Neuroinflammation. 2011 Jun 23;8:72
references: 21699726
references: Cell. 2003 Jul 11;114(1):21-31
references: 12859895
references: Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2868-73
references: 19196977
references: J Virol. 2011 Dec;85(24):12881-9
references: 21976647