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

HIV-infected patients suffer several renal syndromes, which can progress ra pidly from renal insufficiency to end-stage renal disease. Histologically, HIV-induced nephropathy is characterized by prominent tubulopathy with apop tosis of tubular cells. Clinical and experimental evidence suggests that re nal injury may be directly related to virus infection. Although HIV-1 is a polytropic and not solely lymphotropic pathogen, the susceptibility of rena l cells to HIV-1 remains to be determined. This paper demonstrates in vitro the permissiveness of proximal tubular epithelial cells (PTEC) to HIV-1 an d describes the effects of PTEC infection to explain the pathogenesis of tu bular damage in vivo. The results indicate that PTEC express HIV-specific r eceptor and coreceptors and sustain virus replication. We observed that HIV -1 infection causes the death of tubular cells by triggering apr apoptotic pathway involving caspase activation. Fas upregulation but not Fas ligand e xpression was found in the infected PTEC. However, after HIV-1 infection, t ubular cells became susceptible to apoptosis induced through Fas stimulatio n. Caspase inhibition prevented the death of the infected PTEC in spite of persistent viral replication. These findings may explain the prominent hist opathology of HIV-associated nephropathy and demonstrate that the apoptosis of nonlymphoid cells can be directly induced by HIV-1.