title: Renal epithelial cells produce and spread HIV-1 via T-cell contact.
abstract: OBJECTIVE
  Increasing evidence supports the role of the kidney as a reservoir for HIV-1. In-vitro co-cultivation of HIV-infected T cells with renal tubule epithelial (RTE) cells results in virus transfer to the latter, whereas cell-free virus infection is inefficient. We further characterized the fate of HIV-1 after it is internalized in renal epithelial cells.
  
  
  METHODS
  Primary or immortalized CD4 cells were infected with a green fluorescent protein (GFP)-expressing replication competent HIV-1. HIV-1 transfer from T cells to RTE cells was carried out in a co-culture system and evaluated by fluorescence-activated cell sorting analysis. HIV-1 integration in renal cells was evaluated by Alu-PCR and the production of infectious particles was assessed by p24-ELISA and TZM-bl assay. HIV-infected renal cells were used as donor cells in a co-culture system to evaluate their ability to transfer the virus back to T cells.
  
  
  RESULTS
  Renal cells become productively infected by HIV-1 and multiple copies of HIV-1 can be transferred from infected T cells to renal cells. Two separate cell populations were identified among infected renal cells based on reporter gene GFP expression level (low vs. high), only the high showing sensitivity to azidothymidine and ritonavir. Co-cultivation of HIV-1-infected renal cells with noninfected T cells resulted in HIV-1 transmission to T cells, supporting bidirectional exchange of virus between T cells and kidney-derived cells. Persistent expression and generation of infectious virus in renal cells required HIV integration.
  
  
  CONCLUSIONS
  These results support the kidney as a potential reservoir where virus is exchanged between interstitial T cells and RTE cells.
authors: aDuke University Medical Center, Durham, North Carolina bIcahn School of Medicine at Mount Sinai, New York, USA cIstituto Superiore di Sanità, Rome, Italy.
authors: Maria
authors: M
authors: Blasi
authors: Bala
authors: B
authors: Balakumaran
authors: Ping
authors: P
authors: Chen
authors: Donatella R M
authors: DR
authors: Negri
authors: Andrea
authors: A
authors: Cara
authors: Benjamin K
authors: BK
authors: Chen
authors: Mary E
authors: ME
authors: Klotman
mesh_terms: D002478:Cells, Cultured; D018920:Coculture Techniques; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000502:physiology* / Q000821:virology*; D016655:HIV Core Protein p24 / Q000032:analysis; D015497:HIV-1 / Q000254:growth & development / Q000502:physiology*; D006801:Humans; D007668:Kidney / Q000821:virology*; D013601:T-Lymphocytes / Q000502:physiology* / Q000821:virology*; D016662:Virus Integration; D014779:Virus Replication
chemical_list: D016655:HIV Core Protein p24