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Abstract
A NOVEL HIV-1 TRANSGENIC RAT MODEL OF HIV-NEPHROPATHY (HIVAN)
RAY P, LIU X, REID W, HAYNES N, DAVIS H, BRYANT J
HIVAN is associated with proteinuria, focal or segmental glomerulosclerosis, and tubulointerstitial lesions leading to end stage renal disease. Although the pathogenesis is not completely understood, it is believed that HIV-1 plays a direct role in the pathogenesis of this syndrome by infecting renal cells. Here we report that transgenic (Tg) rats carrying a gag-pol deleted HIV -1 provirus under the control of the viral promoter, develop renal lesions resembling those seen in humans with HIVAN. Kidneys from HIV- Tg rats were diffusely pale and enlarged. Many glomeruli showed either segmental or global sclerosis, and enlargement of visceral epithelial cells. The renal tubules showed microcystic tubular dilatation and degeneration, interstitial fibrosis, and mononuclear cell infiltrates. By in situ hybridization, HIV-genes were detected in renal glomerular and tubular epithelial cells, and in mononuclear cells infiltrating the kidney. Immunohistochemistry and flow cytometry studies showed the viral protein gp120 in the circulation and infiltrating mononuclear cells. The early stages of HIVAN were characterized by the induction of renal epithelial and endothelial injury (necrosis and apoptosis) due to the effects of HIV-1 gene products. The late stages of HIVAN were characterized by a renal proliferative response driven by growth factors released by injured epithelial and endothelial cells (i.e., basic Fibroblast Growth Factor). Plasma from HIV-Tg rats with late stage renal disease, but not from control rats or HIV-Tg rats without renal disease, induced the proliferation of cultured human renal glomerular endothelial and epithelial cells. These findings, when interpreted in the context of previous studies, suggest that the infection of renal epithelial cells by HIV-1 and the recruitment of HIV-infected cells in the kindey, play a relevant role in the pathogenesis of HIVAN by inducing renal injury and releasing growth factors from injured renal cells.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
85
Suggested Citation
"RAYP, et al.
A NOVEL HIV-1 TRANSGENIC RAT MODEL OF HIV-NEPHROPATHY (HIVAN).
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
85"
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