TI - 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 . AB - Background The aberrant cell -cycle progression of HIV-1-infected kidney cells plays a major role in the pathogenesis of HIV-associated nephropathy , however the mechanisms whereby HIV-1 induces infected glomerular podocytes or infected tubular epithelium to exit quiescence are largely unknown . Here , we ask whether the expression of HIV-1 genes in infected podocytes induces cyclin D1 and PHOSphorylated pRb (Ser780) expression , hallmarks of cyclin D1-mediated G1 - S phase progression . Results We assessed cyclin D1 and PHOSphorylated pRb (Ser780) expression in two well-characterized models of HIV-associated nephropathy pathogenesis : HIV-1 infection of cultured podocytes and HIV-1 transgenic mice ( Tg26 ) . Compared to controls , cultured podocytes expressing HIV-1 genes and podocytes and tubular epithelium from hyperplastic nephrons in Tg26 kidneys , had increased levels of PHOSphorylated pRb (Ser780) , a target of active cyclin D1/cyclin -dependent kinase-4/6 known to promote G1 - S phase progression . HIV-1-infected podocytes showed markedly elevated cyclin D1 mRNA and cyclin D1 protein , the latter of which did not down-regulate during cell cell contact or differentiation , suggesting post-transcriptional stabilization of cyclin D1 protein levels by HIV-1 . The selective suppression of HIV-1 transcription by the cyclin -dependent kinase inhibitor , flavopiridol , abrogated cyclin D1 expression , underlying the requirement for HIV-1 encoded products to induce cyclin D1 . Indeed , HIV-1 virus deleted of nef failed to induce cyclin D1 mRNA to the level of other single gene mutant viruses . Conclusions HIV-1 expression induces cyclin D1 and PHOSphorylated pRb (Ser780) expression in infected podocytes , suggesting that HIV-1 activates cyclin D1 -dependent cell -cycle mechanisms to promote proliferation of infected renal epithelium .