Update on HIV-associated nephropathy.
OBJECTIVE
HIV-associated nephropathy is characterized by a constellation of pathologic findings including a collapsing glomerulopathy, tubular dilatation, and interstitial infiltration with leukocytes. This review summarizes some of the recent advances in our understanding of the gene products and signaling pathways that contribute to the pathogenesis of HIV-associated nephropathy.


RESULTS
Podocytes infected with HIV-associated nephropathy exhibit podocyte proliferation and de-differentiation. Restriction of HIV-1 transgene expression to the podocyte in a murine model supports the belief that podocyte infection is pivotal to the development of the disease. Recent studies have provided compelling in-vitro and in-vivo evidence that expression of the HIV-1 accessory gene nef is critical in altering the phenotype of mature podocytes and causing injury to these cells. An in-vitro study suggests that nef's effects in the podocyte appear to be mediated through Src kinase-dependent activation of the signal transducer and activator of transcription 3 and mitogen-activated protein kinase 1,2 signaling pathways.


CONCLUSIONS
Recent evidence demonstrates that the viral protein nef plays a critical role in the development of HIV-associated nephropathy and provides a foundation for developing new therapeutic strategies for patients afflicted with this disease.
Shah
Sonal Navin
SN
Mount Sinai School of Medicine, New York, NY 10029, USA.
He
Cijiang John
CJ
Klotman
Paul
P
D016263:AIDS-Associated Nephropathy / Q000235:genetics / Q000378:metabolism* / Q000628:therapy / Q000821:virology; D000818:Animals; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D015693:Gene Products, nef / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D050199:Podocytes / Q000378:metabolism* / Q000821:virology; D050796:STAT3 Transcription Factor / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D054311:nef Gene Products, Human Immunodeficiency Virus; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism
D015693:Gene Products, nef; D050796:STAT3 Transcription Factor; D054311:nef Gene Products, Human Immunodeficiency Virus; D019061:src-Family Kinases; D048049:Extracellular Signal-Regulated MAP Kinases