Simian-human immunodeficiency virus-associated nephropathy in macaques.
A number of chimeric simian-human immunodeficiency virus (SHIV) viruses containing tat, rev, vpu, and env from HIV-1 (strain HXBc2) in a genetic background of simian immunodeficiency virus (SIV(mac)239) have been derived from the parental nonpathogenic SHIV-4 virus. In this article we examine the renal pathology associated with the derivation of these pathogenic SHIV strains. The first of the pathogenic SHIVs, SHIV(KU-1), is associated with rapid CD4(+) T cell loss and opportunistic infections associated with AIDS, but only one of four infected pigtail macaques examined has developed significant renal pathology. The renal pathology in this macaque consists of a diffuse increase in matrix in the core of each lobule with collapsed glomerular capillries, which is similar to the renal changes reported in HIVAN. Passage of this virus into rhesus macaques yielded SHIV(KU-2), which results in renal pathology in three of four inoculated rhesus macaques in which <10% of the glomeruli are involved. A molecular clone of SHIV(KU-2) was derived (SHIV(KU-2MC4)) that causes neurologic and renal pathology with more than 60% of the glomeruli involved and results in uremic level BUN concentrations. These results indicate that SHIV(KU-2MC4) causes severe significant glomerular pathology and should permit a detailed analysis of the molecular determinants associated with the development of SHIV-associated glomerulosclerosis in rhesus macaques.
Stephens
E B
EB
Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City 66160, USA. estephen@kumc.edu
Tian
C
C
Dalton
S B
SB
Gattone
V H
VH
D016263:AIDS-Associated Nephropathy / Q000503:physiopathology / Q000821:virology; D000818:Animals; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D015683:Gene Products, gag / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D007150:Immunohistochemistry; D007668:Kidney / Q000473:pathology; D008253:Macaca mulatta; D008254:Macaca nemestrina; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000472:pathogenicity*
C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D007136:Immunoglobulins; D003094:Collagen