HIV-1 infection initiates an inflammatory cascade in human renal tubular epithelial cells

Michael J. Ross, Cheng Fan, Michael D. Ross, Te Huatearina Chu, Yueyue Shi, Lewis Kaufman, Weijia Zhang, Mary E. Klotman, Paul E. Klotman

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1-11
Number of pages11
JournalJournal of Acquired Immune Deficiency Syndromes
Volume42
Issue number1
DOIs
StatePublished - May 2006
Externally publishedYes

Fingerprint

AIDS-Associated Nephropathy
HIV Infections
HIV-1
Epithelial Cells
Kidney
Infection
Genes
CCAAT-Enhancer-Binding Protein-beta
Inflammation
Vesicular Stomatitis
NF-kappa B
Oligonucleotide Array Sequence Analysis
Chemokines
Transgenic Mice
Chronic Kidney Failure
Up-Regulation
HIV
Cytokines
Viruses
Wounds and Injuries

Keywords

  • Chemokines
  • Epithelium
  • HIV-1
  • Inflammation
  • Kidney
  • Renal failure

ASJC Scopus subject areas

  • Virology
  • Immunology

Cite this

HIV-1 infection initiates an inflammatory cascade in human renal tubular epithelial cells. / Ross, Michael J.; Fan, Cheng; Ross, Michael D.; Chu, Te Huatearina; Shi, Yueyue; Kaufman, Lewis; Zhang, Weijia; Klotman, Mary E.; Klotman, Paul E.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 42, No. 1, 05.2006, p. 1-11.

Research output: Contribution to journalArticle

Ross, Michael J. ; Fan, Cheng ; Ross, Michael D. ; Chu, Te Huatearina ; Shi, Yueyue ; Kaufman, Lewis ; Zhang, Weijia ; Klotman, Mary E. ; Klotman, Paul E. / HIV-1 infection initiates an inflammatory cascade in human renal tubular epithelial cells. In: Journal of Acquired Immune Deficiency Syndromes. 2006 ; Vol. 42, No. 1. pp. 1-11.
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