Infection of human primary renal epithelial cells with HIV-1 from children with HIV-associated nephropathy.
Children affected with human immunodefficiency virus (HIV)-associated nephropathy (HIVAN) usually develop significant renal glomerular and tubular epithelial cell injury. The pathogenesis of these changes is not clearly understood. Human renal tubular epithelial cells (RTEc) do not express CD4 surface receptors, and it is not clear whether these cells can be infected by HIV-1. Certain strains of HIV-1, however, have been shown capable of infecting CD4-negative epithelial cell lines. We hypothesized that the inability of laboratory strains of HIV-1 to infect renal epithelial cells may be due to a limited tropism, as opposed to wild-type viruses derived from children with HIVAN, and that viruses derived from these children are capable of infecting RTEc from the same patient. Here, we have demonstrated that HIV-1 isolates from children with HIVAN can productively infect RTEc through a CD4 independent pathway, and that infected mononuclear cells can transfer the virus to human RTEc. Human RTEc sustained low levels of viral replication and HIV-1 inhibited the growth and survival of cultured human RTEc. Thus, HIV-1 may directly induce degenerative changes in RTEc of children with HIVAN. Infected macrophages may play a relevant role in this process by transferring viruses to RTEc.
Ray
P E
PE
Children's Research Institute, Children's National Medical Center, Washington, D.C., USA. Pray@cnmc.org
Liu
X H
XH
Henry
D
D
Dye
L
L
Xu
L
L
Orenstein
J M
JM
Schuztbank
T E
TE
D016263:AIDS-Associated Nephropathy / Q000473:pathology / Q000821:virology*; D002455:Cell Division; D002478:Cells, Cultured; D002648:Child; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D004848:Epithelium / Q000648:ultrastructure / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification* / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D017403:In Situ Hybridization; D007684:Kidney Tubules / Q000648:ultrastructure / Q000821:virology*; D008264:Macrophages / Q000648:ultrastructure / Q000821:virology; D008854:Microscopy, Electron; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D014779:Virus Replication
D004279:DNA, Viral; D012367:RNA, Viral