INFECTION OF HUMAN PRIMARY RENAL EPITHELIAL-CELLS WITH HIV-1 FROM CHILDREN WITH HIV-ASSOCIATED NEPHROPATHY

Children effected with human immunodefficiency virus (HIV)-associated nephropathy (HIVAN) usually develop significant renal glomerular and t ubular epithelial cell injury. The pathogenesis of these changes is no t clearly understood. Human renal tubular epithelial cells (RTEc) do n ot express CD4 surface receptors, and it is not clear whether these ce lls can be: infected by HIV-1. Certain strains of HIV-1, however, have been shown capable of infecting CD4-negative epithelial cell lines. W e hypothesized that the inability of laboratory strains of HIV-1 to in fect renal epithelial cells may be due to a limited tropism, as oppose d to wild-type viruses derived from children with HIVAN, and that viru ses derived from these children are capable of infecting RTEc from the same patient. Here, we have demonstrated that HIV-1 isolates from chi ldren with HIVAN can productively infect RTEc through a CD4 independen t pathway, and that infected mononuclear cells can transfer the virus to human RTEc. Human RTEc sustained low levels of viral replication an d HIV-1 inhibited the growth and survival of cultured human RTEc. Thus , HIV-1 may directly induce degenerative changes in RTEc of children w ith HIVAN. Infected macrophages may play a relevant role in this proce ss by transferring viruses to RTEc.