HIV-1 kills renal tubular epithelial cells in vitro by triggering an apoptotic pathway involving caspase activation and Fas upregulation

Pier Giulio Conaldi, Luigi Biancone, Antonella Bottelli, Alison Wade-Evans, Lorraine C. Racusen, Mariarosaria Boccellino, Viviana Orlandi, Caterina Serra, Giovanni Camussi, Antonio Toniolo

Research output: Contribution to journalArticlepeer-review

Abstract

HIV-infected patients suffer several renal syndromes, which can progress rapidly from renal insufficiency to end-stage renal disease. Histologically, HIV-induced nephropathy is characterized by prominent tubulopathy with apoptosis of tubular cells. Clinical and experimental evidence suggests that renal injury may be directly related to virus infection. Although HIV-1 is a polytropic and not solely lymphotropic pathogen, the susceptibility of renal cells to HIV-1 remains to be determined. This paper demonstrates in vitro the permissiveness of proximal tubular epithelial cells (PTEC) to HIV-1 and describes the effects of PTEC infection to explain the pathogenesis of tubular damage in vivo. The results indicate that PTEC express HIV-speCifiC receptor and coreceptors and sustain virus replication. We observed that HIV- 1 infection causes the death of tubular cells by triggering an apoptotic pathway involving caspase activation. Fas upregulation but not Fas ligand expression was found in the infected PTEC. However, after HIV-1 infection, tubular cells became susceptible to apoptosis induced through Fas stimulation. Caspase inhibition prevented the death of the infected PTEC in spite of persistent viral replication. These findings may explain the prominent histopathology of HIV-associated nephropathy and demonstrate that the apoptosis of nonlymphoid cells can be directly induced by HIV-1.

Original languageEnglish
Pages (from-to)2041-2049
Number of pages9
JournalJournal of Clinical Investigation
Volume102
Issue number12
Publication statusPublished - Dec 15 1998

Keywords

  • Apoptosis
  • Caspases
  • Fas sensitization
  • HIV-associated nephropathy
  • Tropism

ASJC Scopus subject areas

  • Medicine(all)

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