HIV-1 Vpr activates the DNA damage response in renal tubule epithelial cells.
HIV-associated nephropathy (HIVAN) is a major cause of HIV-related morbidity and mortality. Pathogenesis involves direct infection of the glomerular and tubular epithelial cells leading to characteristic disorder. Recently, we have shown that HIV-1 Vpr causes hypertrophy, hyperploidy, and apoptosis. Here, we report that Vpr activates the DNA damage response resulting in the observed renal phenotype. Renal sections from the HIVAN transgenic mouse model and human biopsies both show an abundant DNA damage response.
Rosenstiel
Paul E
PE
Department of Medicine, Mount Sinai School of Medicine, New York, NY, USA.
Chan
Justin
J
Snyder
Alexander
A
Planelles
Vicente
V
D'Agati
Vivette D
VD
Klotman
Paul E
PE
Klotman
Mary E
ME
D016263:AIDS-Associated Nephropathy / Q000473:pathology*; D000818:Animals; D002460:Cell Line; D004249:DNA Damage; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000821:virology; D016336:Gene Products, vpr / Q000494:pharmacology*; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic
D004279:DNA, Viral; D016336:Gene Products, vpr