title: Virological synapses allow HIV-1 uptake and gene expression in renal tubular epithelial cells.
abstract: In animal models of HIV-associated nephropathy, the expression of HIV regulatory genes in epithelial cells is sufficient to cause disease, but how the CD4-negative epithelial cells come to express HIV genes is unknown. Here, we co-cultured T cells infected with fluorescently tagged HIV with renal tubular epithelial cells and observed efficient virus transfer between these cells. The quantity of HIV transferred was much greater than that achieved by exposure to large amounts of cell-free virus and occurred without a requirement for CD4 or Env. The transfer required stable cell-cell adhesion, which could be blocked by sulfated polysaccharides or poly-anionic compounds. We found that the internalization of virus could lead to de novo synthesis of viral protein from incoming viral RNAs even in the presence of a reverse transcriptase inhibitor. These results illustrate an interaction between infected T cells and nonimmune cells, supporting the presence of virological synapses between HIV-harboring T cells and renal tubular epithelial cells, allowing viral uptake and gene expression in epithelial cells.
authors.affiliation: Mount Sinai School of Medicine, One Gustave Levy Place, New York, NY 10029, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Chen
authors.forename: Arevik
authors.initials: A
authors.lastname: Mosoian
authors.forename: Thomas
authors.initials: T
authors.lastname: Hays
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ross
authors.forename: Paul E
authors.initials: PE
authors.lastname: Klotman
authors.forename: Mary E
authors.initials: ME
authors.lastname: Klotman
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000821:virology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology / Q000821:virology*; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000821:virology*; D011134:Polysaccharides / Q000494:pharmacology; D014779:Virus Replication / Q000502:physiology
chemical_list: D011134:Polysaccharides