title: A single amino acid mutation in the envelope cytoplasmic tail restores the ability of an attenuated simian immunodeficiency virus mutant to deplete mucosal CD4+ T cells.
abstract: Disruption of the conserved motif GYxxØ in the simian immunodeficiency virus (SIV) SIVmac239 envelope (Env) cytoplasmic tail resulted in a virus (ΔGY) that exhibited a high plasma peak but uniquely failed to acutely deplete mucosal CD4(+) T cells. Here, we show that ΔGY containing a flanking S727P mutation that was acquired in ΔGY-infected macaques reacquired the ability to rapidly deplete CD4(+) T cells in lamina propria. This suggests that the GYxxØ motif and S727P each contribute to SIV's targeting to mucosal tissues.
authors.affiliation: Tulane National Primate Research Center, Covington, Louisiana, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Breed
authors.forename: Andrea P O
authors.initials: AP
authors.lastname: Jordan
authors.forename: Pyone P
authors.initials: PP
authors.lastname: Aye
authors.forename: Chie
authors.initials: C
authors.lastname: Sugimoto
authors.forename: Xavier
authors.initials: X
authors.lastname: Alvarez
authors.forename: Marcelo J
authors.initials: MJ
authors.lastname: Kuroda
authors.forename: Bapi
authors.initials: B
authors.lastname: Pahar
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.forename: James A
authors.initials: JA
authors.lastname: Hoxie
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Lackner
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008251:Macaca; D008297:Male; D009092:Mucous Membrane / Q000276:immunology* / Q000821:virology; D020125:Mutation, Missense; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D015686:Gene Products, env
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 8;106(49):20877-82
references.pmid: 19933330
references.citation: PLoS Pathog. 2012;8(5):e1002686
references.pmid: 22693444
references.citation: Immunity. 2010 Jun 25;32(6):737-42
references.pmid: 20620940
references.citation: J Immunol. 2007 Sep 1;179(5):3026-34
references.pmid: 17709517
references.citation: Top HIV Med. 2007 Aug-Sep;15(4):114-7
references.pmid: 17720995
references.citation: J Virol. 2003 Nov;77(21):11708-17
references.pmid: 14557656
references.citation: Am J Pathol. 2010 Sep;177(3):1286-97
references.pmid: 20671267
references.citation: J Immunol. 2008 Nov 15;181(10):6687-91
references.pmid: 18981083
references.citation: Cell Host Microbe. 2011 Jan 20;9(1):46-57
references.pmid: 21238946
references.citation: J Virol. 2001 Jan;75(1):278-91
references.pmid: 11119598
references.citation: J Exp Med. 2004 Sep 20;200(6):761-70
references.pmid: 15365095
references.citation: Curr Opin HIV AIDS. 2011 Sep;6(5):411-8
references.pmid: 21743324
references.citation: Nat Med. 2006 Dec;12(12):1365-71
references.pmid: 17115046
references.citation: PLoS Pathog. 2010 Aug 19;6(8):e1001052
references.pmid: 20808901
references.citation: Science. 2012 Mar 9;335(6073):1188-93
references.pmid: 22403383
references.citation: J Exp Med. 2004 Sep 20;200(6):749-59
references.pmid: 15365096
references.citation: Nature. 2005 Apr 28;434(7037):1093-7
references.pmid: 15793563
references.citation: PLoS Pathog. 2011 Feb;7(2):e1001301
references.pmid: 21383973
references.citation: Nat Med. 2011 Jun 26;17(7):830-6
references.pmid: 21706028
references.citation: Blood. 2007 Feb 1;109(3):1174-81
references.pmid: 17047153
references.citation: Nat Immunol. 2006 Mar;7(3):235-9
references.pmid: 16482171
references.citation: J Virol. 2003 Jun;77(12):6823-35
references.pmid: 12768002
references.citation: J Immunol. 2007 Sep 1;179(5):3035-46
references.pmid: 17709518
references.citation: Dev Comp Immunol. 2008;32(7):859-68
references.pmid: 18304631
references.citation: Science. 1998 Apr 17;280(5362):427-31
references.pmid: 9545219
references.citation: J Virol. 2013 Feb;87(3):1528-43
references.pmid: 23152518
references.citation: Nature. 2005 Apr 28;434(7037):1148-52
references.pmid: 15793562