HUMAN IMMUNODEFICIENCY VIRUS-ASSOCIATED VASCULOPATHY IN TRANSGENIC MICE

There is substantial clinical evidence for the development of vascular disorders in human immunodeficiency virus (HIV)-infected individuals, particularly in the form of vasculitis. Transgenic mice carrying a re plication-defective HIV-1 provirus with selective deletion of the gag, pol, and env genes developed extensive vasculopathy. Restricted expre ssion of HIV nonstructural genes in smooth muscle cells was accompanie d by the migration and proliferation of these cells in blood vessels o f all sizes and at different body sites. The frequent infiltration obs erved in the hypertrophic vessel walls occurred predominantly in the a dventitia and aas composed of primarily T cells and occasionally plasm a cells. The intimal thickening generated significant luminal narrowin g in some vessels, and the restricted blood flow led to ischemia in th e affected tissues. Interestingly, the endothelium did not appear to s upport HIV gene expression or be involved in the pathological process. This transgenic model provides an opportunity to dissect the mechanis m underlying HIV-associated vasculopathy.