title: Cytomegalovirus upregulates expression of CCR5 in central memory cord blood mononuclear cells, which may facilitate in utero HIV type 1 transmission.
abstract: Administration of combination antiretroviral therapy to human immunodeficiency virus type 1 (HIV-1)-infected pregnant women significantly reduces vertical transmission. In contrast, maternal co-opportunistic infection with primary or reactivated cytomegalovirus (CMV) or other pathogens may facilitate in utero transmission of HIV-1 by activation of cord blood mononuclear cells (CBMCs). Here we examine the targets and mechanisms that affect fetal susceptibility to HIV-1 in utero. Using flow cytometry, we demonstrate that the fraction of CD4(+)CD45RO(+) and CD4(+)CCR5(+) CBMCs is minimal, which may account for the low level of in utero HIV-1 transmission. Unstimulated CD4(+) CBMCs that lack CCR5/CD45RO showed reduced levels of HIV-1 infection. However, upon in vitro stimulation with CMV, CBMCs undergo increased proliferation to upregulate the fraction of T central memory cells and expression of CCR5, which enhances susceptibility to HIV-1 infection in vitro. These data suggest that activation induced by CMV in vivo may alter CCR5 expression in CD4(+) T central memory cells to promote in utero transmission of HIV-1.
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Johnson
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Chanie L
authors.initials: CL
authors.lastname: Howard
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Joy
authors.initials: J
authors.lastname: Thurman
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Kyle
authors.initials: K
authors.lastname: Pontiff
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Elan S
authors.initials: ES
authors.lastname: Johnson
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia.
authors.forename: Rana
authors.initials: R
authors.lastname: Chakraborty
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003587:Cytomegalovirus / Q000276:immunology*; D005260:Female; D005312:Fetal Blood / Q000276:immunology*; D005434:Flow Cytometry; D015658:HIV Infections / Q000635:transmission*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D011247:Pregnancy; D019713:Receptors, CCR5 / Q000032:analysis*
chemical_list: C584933:CCR5 protein, human; D019713:Receptors, CCR5
keywords: CCR5; CMV; HIV-1; central memory CD4 cells; cord blood mononuclear cells; mother-to-child transmission
references.citation: Lancet. 1989 Sep 16;2(8664):681
references.pmid: 2570933
references.citation: Immunol Today. 1999 Jul;20(7):330-5
references.pmid: 10379052
references.citation: N Engl J Med. 1995 Mar 30;332(13):833-8
references.pmid: 7870139
references.citation: Proc Natl Acad Sci U S A. 1990 Aug;87(16):6058-62
references.pmid: 2385584
references.citation: Clin Infect Dis. 2014 Mar;58(5):728-35
references.pmid: 24265360
references.citation: Immunol Lett. 2010 Jan 4;127(2):157-8
references.pmid: 19854218
references.citation: J Infect Dis. 2007 Oct 1;196(7):1033-43
references.pmid: 17763326
references.citation: Lancet. 1996 Jan 27;347(8996):213-5
references.pmid: 8551878
references.citation: Hum Immunol. 1997 Oct;57(2):69-79
references.pmid: 9438198
references.citation: J Exp Med. 1997 May 5;185(9):1681-91
references.pmid: 9151905
references.citation: Blood. 2002 Sep 15;100(6):2153-8
references.pmid: 12200380
references.citation: J Virol. 2012 Oct;86(20):11373-9
references.pmid: 22875969
references.citation: AIDS. 1997 Oct;11(12):1479-85
references.pmid: 9342070
references.citation: J Clin Virol. 2008 Mar;41(3):180-5
references.pmid: 18164651
references.citation: Blood. 2005 Feb 15;105(4):1823-7
references.pmid: 15498856
references.citation: N Engl J Med. 2013 Nov 7;369(19):1828-35
references.pmid: 24152233
references.citation: Nature. 1999 Oct 14;401(6754):708-12
references.pmid: 10537110
references.citation: Virology. 2011 Apr 25;413(1):39-46
references.pmid: 21353282
references.citation: J Immunol. 2005 Nov 1;175(9):6117-22
references.pmid: 16237108
references.citation: Science. 1996 Mar 22;271(5256):1723-6
references.pmid: 8596932
references.citation: Retrovirology. 2006 Jun 22;3:35
references.pmid: 16792805
references.citation: J Infect Dis. 2011 Feb 1;203(3):358-63
references.pmid: 21208928
references.citation: Science. 1986 Jul 11;233(4760):215-9
references.pmid: 3014648
references.citation: Proc Natl Acad Sci U S A. 2000 Feb 1;97(3):1269-74
references.pmid: 10655520
references.citation: N Engl J Med. 1999 Jul 8;341(2):77-84
references.pmid: 10395631
references.citation: AIDS. 2009 Oct 23;23(16):2173-81
references.pmid: 19617812
references.citation: Nat Med. 2011 Jun 26;17(7):830-6
references.pmid: 21706028
references.citation: Emerg Infect Dis. 2004 Apr;10(4):643-52
references.pmid: 15200854
references.citation: Pathol Biol (Paris). 1997 Feb;45(2):146-58
references.pmid: 9247037
references.citation: J Virol. 2001 Jan;75(1):83-9
references.pmid: 11119576
references.citation: Nature. 2014 Jan 23;505(7484):509-14
references.pmid: 24356306
references.citation: Pediatr Infect Dis J. 1996 Dec;15(12):1102-6
references.pmid: 8970220
references.citation: J Clin Invest. 2003 Jun;111(11):1747-55
references.pmid: 12782677
references.citation: J Immunol. 2004 Sep 1;173(5):3084-92
references.pmid: 15322168
references.citation: Clin Exp Allergy. 2001 Nov;31(11):1653-6
references.pmid: 11696038
references.citation: Nat Med. 1999 May;5(5):512-7
references.pmid: 10229227
references.citation: Science. 2014 Jan 24;343(6169):428-32
references.pmid: 24356113
references.citation: Hum Reprod. 2011 Dec;26(12):3355-65
references.pmid: 21979962
references.citation: J Acquir Immune Defic Syndr. 2011 Oct 1;58(2):188-92
references.pmid: 21792064
references.citation: J Infect Dis. 2010 Sep 15;202(6):899-907
references.pmid: 20687848
references.citation: Virology. 2012 Mar 30;425(1):23-30
references.pmid: 22280894