HIV/AIDS Nephropathy: Mechanisms of Virus-Induced Cell Cycle Disruption Elucidated

US researchers have shed new light on the processes that lead to the development of kidney dysfunction in HIV patients. "The aberrant cell-cycle progression of HIV-1 infected kidney cells plays a major role in the pathogenesis of HIV-associated nephropathy," explained Peter J. Nelson and colleagues at Mount Sinai School of Medicine in New York City. "However, the mechanisms whereby HIV-1 induces infected glomerular podocytes or infected tubular epithelium to exit quiescence are largely unknown."

Nelson and coauthors found that HIV genes trigger the expression of cyclin D1 and other cell cycle-associated protein by podocytes. The researchers examined podocyte cell cultures and transgenic mice infected with HIV. Podocytes that expressed HIV genes in vitro or in vivo showed a significant upregulation of cyclin D1 mRNA and protein, the report stated.

Study data also showed that infected podocytes expressed phospho-pRb (Ser780) at elevated levels. The protein has been linked to cyclin D1-induced G1-to-S phase cell cycle progression.

The cyclin-dependent kinase inhibitor flavopiridol prevented both HIV gene transcription and cyclin D1 expression, the authors stated. Their full report, "HIV-1 Expression Induces Cyclin D1 Expression and pRb Phosphorylation in Infected Podocytes: Cell-Cycle Mechanisms Contributing to the Proliferative Phenotype in HIV-Associated Nephropathy," is published in the September issue of BioMed Central Microbiology (2002;2:26).

"HIV expression induces cyclin D1 and phospho-pRb (Ser780) expression in infected podocytes," Nelson and colleagues concluded, "suggesting that HIV-1 activates cyclin D1-dependent cell-cycle mechanisms to promote proliferation of infected renal epithelium."

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