SIV-Associated Nephropathy in Rhesus Macaques Infected with Lymphocyte-Tropic SIVmac239

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Abstract
We examined the renal pathology and viral genetic changes following inoculation of six rhesus macaques with lymphocyte-tropic SIVmac239. Portions of the renal cortex were sieved into glomerular and tubulointerstitial (TI) fractions and examined for SIVmac sequences by PCR and for p27 core antigen. SIVmac sequences were detected in renal tissue from five of six macaques (three of five glomerular and five of five TI fractions were positive for SIV by PCR). Glomerulosclerosis (segmental and global) was evident in two macaques that were positive for env sequences in the glomerular fractions. Diffuse mesangial hyperplasia and matrix expansion were present in all three animals with glomerular SIV, as was an increase in glomerular collagen I and collagen IV. Tubulointerstitial inflammation was evident in all virus-inoculated macaques. The TI infiltration of CD68+ cells was most pronounced in the animals with SIVmac present in the glomerulus. All SIVmac-infected macaques exhibited increased glomerular deposition of IgM and to a lesser extent IgG, but no C3 or IgA was evident. Sequence analyses of the viral env gene (gp120) isolated from the glomerular and TI fractions of a macaque that developed glomerulopathy revealed the presence of specific viral variants in glomerular and TI fractions. In addition, chimeric viruses constructed with glomerular but not tubulointerstitial gp120 sequences were converted to a macrophage-tropic phenotype. These results indicate that infection by lymphocyte-tropic SIVmac239 is primarily associated with immunoglobulin deposition in the glomerulus and suggests that when glomerulosclerosis develops there is selection of viral variants that are macrophage tropic in nature.