We previously showed that inoculation of rhesus macaques with molecularly cloned lymphocytetropic simian immunodeficiency virus (SIVmac239) results in SIV-associated nephropathy (SIVAN) and that the glomerulosclerotic lesions were associated with the selection of macrophagetropic (M-tropic) variants (V. H. Gattone et al.,
AIDS Res. Hum. Retroviruses 14:1163-1180, 1998). In the present study, seven rhesus macaques were inoculated with M-tropic SIVmacR71/17E, and the renal pathology was examined at necropsy. All SIVmacR71/17E-infected macaques developed
AIDS, and most developed other systemic complications, including SIV-induced
encephalitis and lentivirus
interstitial pneumonia. There was no correlation between the length of
infection (42 to 97 days), circulating CD4(+) T-cell counts, and renal disease. Of the seven macaques inoculated with SIVmacR71/17E, five developed significant mesangial
hyperplasia and expansion of matrix and four were clearly azotemic (serum
urea nitrogen concentration of 40 to 112 mg/dl). These same five macaques developed focal segmental to global glomerulosclerotic lesions. Increased numbers of glomerular CD68(+) cells (monocytes/macrophages) were found in glomeruli but not the tubulointerstitium of the macaques inoculated with SIVmacR71/17E. All macaques had glomerular deposits of
immunoglobulin G (
IgG),
IgM, and tubuloreticular inclusions, and six of seven had
IgA deposition. However, there was no correlation between the presence of circulating anti-SIVmac
antibodies,
immunoglobulin deposition, and glomerular disease. Tubulointerstitial infiltrates were mild, with little or no correlation to
azotemia, while microcystic tubules were evident in those with glomerulosclerosis or
azotemia. The four most severely affected macaques were positive for diffuse glomerular immunostaining for viral core
p27 antigen, and there was intense staining in the glomeruli of the two macaques with the most severe glomerulosclerosis. Viral sequences were isolated from glomerular and tubulointerstitial fractions from macaques with severe glomerulosclerosis but only from the tubulointerstitial compartment of those that did not develop glomerulosclerosis. Interviral recombinant viruses generated with env sequences isolated from glomeruli confirmed the M-tropic nature of the virus found in the glomeruli. The correlation between the increased number of CD68(+) cells (monocytes/macrophages) in the glomeruli, the localization of
p27 antigen in the glomeruli, and the glomerular pathology confirms and extends our previous observations of an association between glomerular
infection and infiltration by M-tropic virus and SIVAN.