HIV-1 infection initiates an inflammatory cascade in human renal tubular epithelial cells.
HIV-associated nephropathy (HIVAN) is the most common cause of chronic renal failure in HIV-infected patients. Tubulointerstitial inflammation is a prominent component of the histopathology of HIVAN. The pathogenesis of HIVAN is a result of infection of renal epithelial cells, but the cellular response to this infection remains poorly defined. In these studies, we used oligonucleotide microarrays to identify differentially expressed genes in renal tubular epithelial cells from a patient with HIVAN at three time points after infection with vesicular stomatitis virus-pseudotyped gag/pol-deleted HIV-1. Very few genes were differentially expressed 12 and 24 hours after infection. Three days after infection, however, 47 genes were upregulated by at least 1.8-fold. The most prominent response of these cells to HIV-1 expression was production of proinflammatory mediators, including chemokines, cytokines, and adhesion molecules. Many of the upregulated genes are targets of interleukin 6 and nuclear factor kappa B regulation, suggesting a central role for these proteins in the response of tubular epithelial cells to HIV-1 infection. Analysis of kidneys from HIV-1 transgenic mice revealed upregulation of many of the proinflammatory genes identified in the microarray studies. These studies provide novel insights into the mechanisms by which HIV-1 infection of tubular epithelial cells leads to tubulointerstitial inflammation and progressive renal injury.
Ross
Michael J
MJ
Division of Nephrology, Mount Sinai School of Medicine, New York, NY 10029, USA. michael.ross@mssm.edu
Fan
Cheng
C
Ross
Michael D
MD
Chu
Te-Huatearina
TH
Shi
Yueyue
Y
Kaufman
Lewis
L
Zhang
Weijia
W
Klotman
Mary E
ME
Klotman
Paul E
PE
D016263:AIDS-Associated Nephropathy / Q000378:metabolism*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D015685:Fusion Proteins, gag-pol / Q000235:genetics; D020869:Gene Expression Profiling; D015658:HIV Infections / Q000378:metabolism* / Q000473:pathology; D015497:HIV-1 / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007684:Kidney Tubules; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011533:Proviruses / Q000235:genetics; D016865:Reassortant Viruses / Q000235:genetics; D013997:Time Factors; D015854:Up-Regulation; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics
D015815:Cell Adhesion Molecules; D016207:Cytokines; D015685:Fusion Proteins, gag-pol