title: Transcytosis of Human immunodeficiency virus 1 across the placenta is enhanced by treatment with tumour necrosis factor alpha.
abstract: The human placenta is relatively resistant to Human immunodeficiency virus 1 (HIV-1), but obstetric complications associated with inflammatory processes, including chorioamnionitis and spontaneous preterm delivery, are associated with increased rates of vertical transmission. It was hypothesized that the pro-inflammatory mediator tumour necrosis factor alpha (TNF-alpha), which promotes HIV-1 transmission across endothelial membranes, increases HIV-1 transmission across the placenta. Flow cytometry and immunostaining studies were performed, which demonstrated that the HIV-1 receptors CD4, CCR5 and CXCR4 were not expressed by villous trophoblast cells. Consequently, primary villous trophoblast cells were not infected with cell-free HIV-1 isolates, as measured by in situ PCR and quantitative PCR, but villous trophoblast cells were infected by HIV-1-infected peripheral blood mononuclear cells (PBMC). HIV-1 from infected PBMC was rapidly transported across confluent transformed trophoblast cell monolayers by transcytosis, and TNF-alpha significantly upregulated transcytosis of HIV-1 across the trophoblast layer without disrupting cell viability or confluency. Inhibitors of TNF-alpha (antibodies against TNF-alpha and TNF-alpha receptors) and an anti-inflammatory drug (tenidap) significantly reduced transcytosis rates. It was concluded that the villous trophoblast is resistant to infection by cell-free HIV-1 but susceptible to transcytosis of HIV-1 from infected PBMC, and inflammatory mediators such as TNF-alpha may play a critical role in promoting maternal-fetal transmission of HIV-1.
authors.affiliation: Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, 1352 Biomedical Research Building II/III, 421 Curie Boulevard, Philadelphia, PA 19104-6142, USA.
authors.forename: Samuel
authors.initials: S
authors.lastname: Parry
authors.affiliation: Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, 1352 Biomedical Research Building II/III, 421 Curie Boulevard, Philadelphia, PA 19104-6142, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, Tokyo Medical and Dental University, Tokyo 113, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Koi
authors.affiliation: Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, 1352 Biomedical Research Building II/III, 421 Curie Boulevard, Philadelphia, PA 19104-6142, USA.
authors.forename: Fabian
authors.initials: F
authors.lastname: Arechavaleta-Velasco
authors.affiliation: Center for Research on Reproduction and Women's Health, University of Pennsylvania School of Medicine, 1352 Biomedical Research Building II/III, 421 Curie Boulevard, Philadelphia, PA 19104-6142, USA.
authors.forename: Michal A
authors.initials: MA
authors.lastname: Elovitz
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015704:CD4 Antigens / Q000032:analysis; D002460:Cell Line; D002478:Cells, Cultured; D005434:Flow Cytometry; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000276:immunology / Q000635:transmission; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007211:Indoles / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000821:virology*; D000078183:Oxindoles; D010920:Placenta / Q000821:virology*; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D019713:Receptors, CCR5 / Q000032:analysis; D019718:Receptors, CXCR4 / Q000032:analysis; D014327:Trophoblasts / Q000737:chemistry / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015704:CD4 Antigens; D016655:HIV Core Protein p24; D007211:Indoles; D000078183:Oxindoles; D012367:RNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D014409:Tumor Necrosis Factor-alpha; C062866:tenidap