HIV-1 Vpr inhibits cytokinesis in human proximal tubule cells.

Published

Journal Article

Transgenic mouse models of HIV-associated nephropathy (HIVAN) show that expression of HIV-1 genes in kidney cells produces collapsing focal segmental glomerulosclerosis and microcystic tubular disease typical of the human disease. HIV-1 vpr plays an important role in the glomerulosclerosis of HIVAN, especially when it is associated with nef expression in podocytes. Further, Vpr is reported to exacerbate tubular pathology. Here we determined effects of vpr expression on renal tubular epithelial cell function by transducing them with a pseudotyped lentivirus vector carrying HIV-1 vpr and control genes. Vpr expression in the cultured cells impaired cytokinesis causing cell enlargement and multinucleation. This profound in vitro phenotype caused us to reexamine the HIVAN mouse model and human HIVAN biopsies to see if similar changes occur in vivo. Both showed abundant hypertrophic tubule cells similar to the in vitro finding that represents a previously unappreciated aspect of the human disease. Additionally, multinucleated tubular cells were identified in the murine HIVAN model and increased chromosome number was detected in tubular cells of human HIVAN biopsies. Our study provides evidence of a new clinical phenotype in HIVAN that may result from the ability of Vpr to impair cytokinesis.

Full Text

Duke Authors

Cited Authors

  • Rosenstiel, PE; Gruosso, T; Letourneau, AM; Chan, JJ; LeBlanc, A; Husain, M; Najfeld, V; Planelles, V; D'Agati, VD; Klotman, ME; Klotman, PE

Published Date

  • October 2008

Published In

Volume / Issue

  • 74 / 8

Start / End Page

  • 1049 - 1058

PubMed ID

  • 18614999

Pubmed Central ID

  • 18614999

Electronic International Standard Serial Number (EISSN)

  • 1523-1755

Digital Object Identifier (DOI)

  • 10.1038/ki.2008.303

Language

  • eng

Conference Location

  • United States