Microcyst formation and HIV-1 gene expression occur in multiple nephron segments in HIV-associated nephropathy

Tubular microcyst formation is a prominent histopathologic feature of HIV-a ssociated nephropathy (HIVAN), but its pathogenesis is unknown. HIV-1 has r ecently been shown to infect renal tubular epithelial cells in patients wit h HIVAN. In addition, HIV-1 gene expression in renal epithelial cells has b een shown to cause a renal disease that is identical to HIVAN in HIV-1 tran sgenic mice. In these studies, immunohistochemistry for tubular segment-spe cific markers and mRNA in situ hybridization for HIV-1 was used to determin e which tubular segments develop microcysts and which segments express HIV- 1 in the kidneys of transgenic mice and patients with HIVAN. It was found t hat microcysts involve multiple nephron segments in both patients with HIVA N and HIV-1 transgenic mice. Furthermore, HIV-1 infection in HIVAN and HIV- 1 transgene expression also occurs in multiple segments of the nephron. The se data support a direct role for HIV-1 infection of renal epithelial cells in the pathogenesis of microcyst formation in patients with HIVAN.