Expression of HIV-1 genes in podocytes alone can lead to the full spectrum of HIV-1-associated nephropathy

Kidney Int. 2005 Sep;68(3):1048-60. doi: 10.1111/j.1523-1755.2005.00497.x.


Background: Human immunodeficiency virus (HIV)-1-associated nephropathy (HIVAN) is characterized by collapsing focal and segmental glomerulosclerosis (FSGS) and microcystic tubular dilatation. HIV-1 infection is also associated with other forms of nephropathy, including mesangial hyperplasia. Since HIV-1 gene products are detected in podocytes and other renal cells, it remains uncertain whether podocyte-restricted HIV-1 gene expression can account for the full spectrum of renal lesions involving nonpodocytes.

Methods: To define the role of podocyte-restricted HIV-1 gene expression in the progression of HIVAN, we generated transgenic mice that express nonstructural HIV-1 genes selectively in podocytes.

Results: Four of the seven founder mice developed proteinuria and nephropathy. In a subsequently established transgenic line, reverse transcription-polymerase chain reaction (RT-PCR) analysis detected mRNAs for vif, vpr, nef, and spliced forms of tat and rev, but not vpu, in the kidney. In situ hybridization localized HIV-1 RNA to the podocyte. Transgenic mice on FVB/N genetic background exhibited cuboidal morphology of podocytes with reduced extension of primary and foot processes at 2 weeks of age. After 3 weeks of age, these mice developed massive and nonselective proteinuria with damage of podocytes and other glomerular cells and, after 4 weeks of age, collapsing FSGS and microcystic tubular dilatation. In marked contrast, transgenic mice with C57BL/6 genetic background showed either normal renal histology or only mild mesangial expansion without overt podocyte damage.

Conclusion: The present study demonstrates that podocyte-restricted expression of HIV-1 gene products is sufficient for the development of collapsing glomerulosclerosis in the setting of susceptible genetic background.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • AIDS-Associated Nephropathy / genetics
  • AIDS-Associated Nephropathy / physiopathology*
  • AIDS-Associated Nephropathy / virology*
  • Animals
  • Female
  • Gene Expression Regulation, Viral
  • Genetic Predisposition to Disease
  • HIV-1 / genetics*
  • Male
  • Membrane Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nephrotic Syndrome / genetics
  • Nephrotic Syndrome / physiopathology
  • Nephrotic Syndrome / virology
  • Podocytes / pathology
  • Podocytes / physiology*
  • Podocytes / virology*
  • Promoter Regions, Genetic
  • Transgenes / genetics


  • Membrane Proteins
  • nephrin