title: R5- and X4-HIV-1 use differentially the endometrial epithelial cells HEC-1A to ensure their own spread: implication for mechanisms of sexual transmission.
abstract: The mechanism of viral transmission across the mucosal barrier is poorly understood. Using the endometrial epithelium-derived cell line HEC-1A, we found that the cells are capable of sequestering large numbers of HIV-1 particles but are refractory to cell-free viral infection. The removal of heparan sulfate moieties of cell-surface proteoglycans (HSPG) from the apical pole of HEC-1A accounted for at least 60% of both R5- and X4-HIV-1 attachment, showing their important implication in viral attachment. HEC-1A cells also have the capacity to endocytose a weak proportion of the attached virus and pass it along to underlying cells. Fucose, N-acetylglucosamine and mannosylated-residues inhibited the transcytosis of some virus isolates, suggesting that mannose receptors can be implicated on the both R5- and X4-HIV-1 transcytosis. The inhibition of HIV transcytosis by blocking CCR5 mAb suggests the implication of specific interaction between the viral gp120 and sulfated moiety of syndecans during the transcytosis of mostly R5- and X4-HIV-1. At the basolateral pole of HEC-1A, HSPG sequestered X4- and not R5-HIV-1, highlighting the important role of HEC-1A as an X4 virus reservoir. The cell-free virus particles that have transcytosed could infect activated T cells but with a weaker efficiency than virus that had not transcytosed. The specific stimulation of HEC-1A by R5-HIV-1 increased the release of monocytes/chemokines-attracting chemokines (IL-8 and GR0) and proinflammatory cytokines (TNF-beta and IL-1alpha) that enhanced the production of virus by activated T cells. This study suggests that R5 and X4 viruses can differentially use epithelial cells to ensure their own spread.
authors.affiliation: Unité INSERM U743 Equipe Immunité et Biothérapie Muqueuse, Centre de Recherches Biomédicales des Cordeliers, Paris, Cedex 06, France. hela.saidi@u430.bhdc.jussieu.fr <hela.saidi@u430.bhdc.jussieu.fr>
authors.forename: Héla
authors.initials: H
authors.lastname: Saïdi
authors.forename: Giuliana
authors.initials: G
authors.lastname: Magri
authors.forename: Nadine
authors.initials: N
authors.lastname: Nasreddine
authors.forename: Mary
authors.initials: M
authors.lastname: Réquena
authors.forename: Laurent
authors.initials: L
authors.lastname: Bélec
mesh_terms: D000117:Acetylglucosamine / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000494:pharmacology; D065100:CCR5 Receptor Antagonists; D002460:Cell Line; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000096:biosynthesis; D004705:Endocytosis / Q000187:drug effects; D004717:Endometrium / Q000821:virology*; D004847:Epithelial Cells / Q000821:virology*; D005260:Female; D005643:Fucose / Q000494:pharmacology; D016655:HIV Core Protein p24 / Q000032:analysis; D015658:HIV Infections / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology*; D019812:Heparan Sulfate Proteoglycans / Q000502:physiology; D006801:Humans; D053582:Interleukin-1alpha / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D037181:Lectins, C-Type / Q000502:physiology; D008358:Mannose / Q000031:analogs & derivatives / Q000494:pharmacology; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins / Q000502:physiology; D019713:Receptors, CCR5 / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014774:Virulence; D053585:Virus Attachment
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D016655:HIV Core Protein p24; D019812:Heparan Sulfate Proteoglycans; D053582:Interleukin-1alpha; D016209:Interleukin-8; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011956:Receptors, Cell Surface; D014409:Tumor Necrosis Factor-alpha; D005643:Fucose; D008358:Mannose; D000117:Acetylglucosamine