title: HIV-1 Vpu mediated downregulation of CD155 requires alanine residues 10, 14 and 18 of the transmembrane domain.
abstract: HIV-1 NL4-3 Vpu induces downregulation of cell surface CD155, a ligand for the DNAM-1 activating receptor of NK and CD8(+) T cells, to evade NK cell mediated immune response. Here we show that the conserved alanine residues at positions 10, 14 and 18 in the TM domain of Vpu are required for the efficient downregulation of cell surface CD155. In contrast, the CK-2 phosphorylation sites and the second α-helix in the cytoplasmic Vpu domain have no influence on the surface expression of CD155. Thus, compared to Vpu׳s effect on CD4, NTB-A and tetherin, the Vpu mediated downregulation of CD155 is an independent Vpu function. We finally show that in contrast to other lentiviral strains, only Vpu and Nef from HIV-1 M NL4-3 potently interfere with CD155 surface expression. Thus, Vpu seems to subvert NK cell responses against HIV-1 infected T cells by modulation of receptors necessary for NK cell activation.
authors.affiliation: Institute of Virology, University of Erlangen-Nuremberg, Germany; Institute of Virology, Helmholtz Zentrum Munich, Germany. Electronic address: sebastian.bolduan@helmholtz-muenchen.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bolduan
authors.affiliation: Institute of Virology, University of Erlangen-Nuremberg, Germany. Electronic address: tatjana.reif@viro.med.uni-erlangen.de.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Reif
authors.affiliation: Institute of Virology, Helmholtz Zentrum Munich, Germany; Institute of Medical Virology and Epidemiology of Viral Diseases, University Clinic Tübingen, Germany. Electronic address: michael.schindler@helmholtz-muenchen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Schindler
authors.affiliation: Institute of Virology, University of Erlangen-Nuremberg, Germany. Electronic address: ulrich.schubert@viro.med.uni-erlangen.de.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Schubert
mesh_terms: D000409:Alanine / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D002462:Cell Membrane / Q000378:metabolism / Q000821:virology; D015536:Down-Regulation; D015658:HIV Infections / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D054298:Human Immunodeficiency Virus Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000235:genetics* / Q000378:metabolism; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000086082:Viroporin Proteins
chemical_list: D000409:Alanine; D054298:Human Immunodeficiency Virus Proteins; D011991:Receptors, Virus; D054334:Viral Regulatory and Accessory Proteins; C066100:poliovirus receptor; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins
keywords: CD155; HIV-1; Nef; SIV; Vpu
references.citation: J Gen Virol. 2013 Dec;94(Pt 12):2664-2669
references.pmid: 24045107
references.citation: mBio. 2011 May 24;2(3):e00036-11
references.pmid: 21610122
references.citation: J Virol. 2010 Dec;84(24):12958-70
references.pmid: 20926557
references.citation: J Biol Chem. 2009 Dec 11;284(50):35060-72
references.pmid: 19837671
references.citation: J Virol. 1998 Mar;72(3):2280-8
references.pmid: 9499087
references.citation: Nat Rev Mol Cell Biol. 2008 Aug;9(8):603-15
references.pmid: 18648374
references.citation: Nature. 1988 Aug 11;334(6182):532-4
references.pmid: 3043230
references.citation: J Virol. 2011 Oct;85(19):9737-48
references.pmid: 21775465
references.citation: Virology. 2011 Mar 1;411(1):65-77
references.pmid: 21237475
references.citation: AIDS Res Hum Retroviruses. 2005 May;21(5):379-94
references.pmid: 15929700
references.citation: AIDS. 2009 Jun 1;23(9):1077-87
references.pmid: 19424050
references.citation: Cell Host Microbe. 2008 Apr 17;3(4):245-52
references.pmid: 18342597
references.citation: J Virol. 2009 Aug;83(15):7536-46
references.pmid: 19474106
references.citation: Nature. 1970 Aug 15;227(5259):680-5
references.pmid: 5432063
references.citation: PLoS Pathog. 2010 Apr 29;6(4):e1000869
references.pmid: 20442859
references.citation: J Virol. 1993 Aug;67(8):5056-61
references.pmid: 8331740
references.citation: J Virol. 1992 Dec;66(12):7193-200
references.pmid: 1433512
references.citation: Immunity. 1999 Jun;10(6):661-71
references.pmid: 10403641
references.citation: J Biol Chem. 2012 Jan 2;287(1):58-67
references.pmid: 22072710
references.citation: J Virol. 2006 Aug;80(16):8047-59
references.pmid: 16873261
references.citation: Cell Host Microbe. 2009 Nov 19;6(5):409-21
references.pmid: 19917496
references.citation: PLoS Pathog. 2009 Oct;5(10):e1000613
references.pmid: 19798433
references.citation: J Virol. 2003 Oct;77(19):10548-56
references.pmid: 12970439
references.citation: J Gen Virol. 2007 Jan;88(Pt 1):242-250
references.pmid: 17170457
references.citation: J Virol. 2009 May;83(9):4574-90
references.pmid: 19244337
references.citation: Proc Natl Acad Sci U S A. 2003 May 13;100(10):5783-8
references.pmid: 12724521
references.citation: Nature. 2008 Jan 24;451(7177):425-30
references.pmid: 18200009
references.citation: Virology. 2011 Jul 20;416(1-2):75-85
references.pmid: 21601230
references.citation: Retrovirology. 2010 Jan 15;7:1
references.pmid: 20078884
references.citation: J Virol. 2012 Apr;86(8):4496-504
references.pmid: 22301152
references.citation: Retrovirology. 2011 Dec 15;8:103
references.pmid: 22171785
references.citation: Retrovirology. 2007 Oct 15;4:75
references.pmid: 17937819
references.citation: Immunity. 1996 Jun;4(6):573-81
references.pmid: 8673704
references.citation: Cell Host Microbe. 2010 Nov 18;8(5):397-409
references.pmid: 21075351
references.citation: PLoS Pathog. 2010 Apr 08;6(4):e1000856
references.pmid: 20386718
references.citation: Virology. 2013 Jun 5;440(2):190-203
references.pmid: 23528733
references.citation: PLoS One. 2010 Feb 22;5(2):e9344
references.pmid: 20179761
references.citation: Nat Immunol. 2011 Aug 28;12(10):975-83
references.pmid: 21874023
references.citation: Science. 1988 Sep 2;241(4870):1221-3
references.pmid: 3261888
references.citation: J Virol. 1990 Feb;64(2):621-9
references.pmid: 2404139