title: HIV infection-induced transcriptional program in renal tubular epithelial cells activates a CXCR2-driven CD4+ T-cell chemotactic response.
abstract: Viral replication and interstitial inflammation play important roles in the pathogenesis of HIV-associated nephropathy. Cell-cell interactions between renal tubule epithelial cells (RTECs) and HIV-infected T cells can trigger efficient virus internalization and viral gene expression by RTEC. To understand how HIV replication initiates HIV-associated nephropathy, we studied the cellular response of RTECs to HIV, examining the transcriptional profiles of primary RTECs exposed to cell-free HIV or HIV-infected T cells.
  
  
  
  HIV-induced gene expression in hRTECs was examined in vitro by Illumina RNA deep sequencing and revealed an innate response to HIV, which was subclassified by gene ontology biological process terms. Chemokine responses were examined by CD4 T-cell chemotaxis assays.
  
  
  
  As compared with cell-free virus infection, exposure to HIV-infected T cells elicited a stronger upregulation of inflammatory and immune response genes. A major category of upregulated genes are chemokine/cytokine families involved in inflammation and immune response, including inflammatory cytokines CCL20, IL6 and IL8-related chemokines: IL8, CXCL1, CXCL2, CXCL3, CXCL5 and CXCL6. Supernatants from virus-exposed RTECs contained strong chemoattractant activity on primary CD4 T cells, which was potently blocked by a CXCR2 antagonist that antagonizes IL8-related chemokines. We observed a preferential migration of CXCR2-expressing, central memory CD4 T cells in response to HIV infection of RTECs.
  
  
  
  Interactions between primary RTECs and HIV-infected T cells result in potent induction of inflammatory response genes and release of cytokines/chemokines from RTECs that can attract additional T cells. Activation of these genes reflects an innate response to HIV by nonimmune cells.
authors.affiliation: aDivision of Infectious Diseases, Department of Medicine, Icahn School of Medicine at Mount Sinai bBioinformatics Core, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York cDepartment of Medicine, Duke University Medical Center, Durham, North Carolina, USA. *These authors contributed equally to this work.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Zhengzi
authors.initials: Z
authors.lastname: Yi
authors.forename: Weijia
authors.initials: W
authors.lastname: Zhang
authors.forename: Mary E
authors.initials: ME
authors.lastname: Klotman
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Chen
mesh_terms: D016263:AIDS-Associated Nephropathy / Q000503:physiopathology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002478:Cells, Cultured; D002633:Chemotaxis; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology*; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D007155:Immunologic Factors / Q000096:biosynthesis*; D007684:Kidney Tubules / Q000378:metabolism*; D023063:Receptors, Interleukin-8B / Q000378:metabolism
chemical_list: D007155:Immunologic Factors; D023063:Receptors, Interleukin-8B