title: Reduced ability of newborns to produce CCL3 is associated with increased susceptibility to perinatal human immunodeficiency virus 1 transmission.
abstract: The role of CC chemokines in protection against mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission is not well understood. It was observed that mitogen-induced production of CCL3 and CCL4 by cord-blood mononuclear cells was increased among infants born to HIV-positive compared with HIV-negative mothers, and that a deficiency in production of CCL3 was associated with increased susceptibility to intrapartum HIV-1 infection. CCL3-L1 gene copy number was associated with CCL3 production and with vertical transmission. However, at equivalent CCL3-L1 gene copy numbers, infants who acquired HIV-1 infection relative to their exposed but uninfected counterparts had lower production of CCL3, suggesting that they may harbour some non-functional copies of this gene. Nucleotide changes that may influence CCL3 production were evident in the CCL3 and CCL3-L1 genes upstream of exon 2. Our findings suggest that infants who display a deficient-production phenotype of CCL3 are at increased risk of acquiring HIV-1, indicating that this chemokine in particular plays an essential role in protective immunity.
authors.affiliation: AIDS Virus Research Unit, National Institute for Communicable Diseases, and Department of Virology, University of the Witwatersrand, Private Bag X4, Sandringham, Johannesburg 2131, South Africa.
authors.forename: Stephen
authors.initials: S
authors.lastname: Meddows-Taylor
authors.affiliation: AIDS Virus Research Unit, National Institute for Communicable Diseases, and Department of Virology, University of the Witwatersrand, Private Bag X4, Sandringham, Johannesburg 2131, South Africa.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Donninger
authors.affiliation: AIDS Virus Research Unit, National Institute for Communicable Diseases, and Department of Virology, University of the Witwatersrand, Private Bag X4, Sandringham, Johannesburg 2131, South Africa.
authors.forename: Maria
authors.initials: M
authors.lastname: Paximadis
authors.affiliation: AIDS Virus Research Unit, National Institute for Communicable Diseases, and Department of Virology, University of the Witwatersrand, Private Bag X4, Sandringham, Johannesburg 2131, South Africa.
authors.forename: Diana B
authors.initials: DB
authors.lastname: Schramm
authors.affiliation: AIDS Virus Research Unit, National Institute for Communicable Diseases, and Department of Virology, University of the Witwatersrand, Private Bag X4, Sandringham, Johannesburg 2131, South Africa.
authors.forename: Fiona S
authors.initials: FS
authors.lastname: Anthony
authors.affiliation: Perinatal HIV Research Unit, Chris Hani Baragwanath Hospital, Soweto, South Africa.
authors.forename: Glenda E
authors.initials: GE
authors.lastname: Gray
authors.affiliation: Gertrude H. Sergievsky Centre, College of Physicians and Surgeons, and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA.
authors.forename: Louise
authors.initials: L
authors.lastname: Kuhn
authors.affiliation: AIDS Virus Research Unit, National Institute for Communicable Diseases, and Department of Virology, University of the Witwatersrand, Private Bag X4, Sandringham, Johannesburg 2131, South Africa.
authors.forename: Caroline T
authors.initials: CT
authors.lastname: Tiemessen
mesh_terms: D001483:Base Sequence; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D015331:Cohort Studies; D004247:DNA / Q000235:genetics; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D018628:Gene Dosage; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission*; D018023:HIV Seronegativity / Q000276:immunology; D015497:HIV-1; D006801:Humans; D066298:In Vitro Techniques; D007223:Infant; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000097:blood; D008934:Mitogens / Q000494:pharmacology; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy
chemical_list: C492767:CCL3L1 protein, human; C066507:CCL4 protein, human; C483024:CCL5 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D008934:Mitogens; D004247:DNA