-- Researchers in the United States 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. Murphy 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."
Murphy and coauthors found that HIV genes trigger the expression of cyclin D1 and other cell cycle-associated proteins 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, according to the report.
In addition, infected podocytes expressed phospho-pRb (Ser780) at elevated levels, study data showed. This 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 (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. BioMed Central Microbiology, 2002;2:26).
"HIV-1 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."
The corresponding author for this report is Peter J. Nelson, Division of Nephrology, Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1243, New York, NY 10029, USA. E-mail: firstname.lastname@example.org.
Key points reported in this study include:
HIV-infected podocytes express heightened levels of cyclin D1
Infected podocytes also upregulated phospho-pRb (Ser780), a protein linked to cyclin D1-induced G1-to-S cell cycle progression
These effects may be part of the pathogenesis of HIV-associated nephropathy
This article was prepared by AIDS Weekly editors from staff and other reports.