RHESUS MACAQUES INFECTED WITH MACROPHAGE-TROPIC SIMIAN IMMUNODEFICIENCY VIRUS (SIV(MAC)R71 17E) EXHIBIT EXTENSIVE FOCAL SEGMENTAL AND GLOBAL GLOMERULOSCLEROSIS/

We previously showed that inoculation of rhesus macaques with molecula rly cloned lymphocytetropic simian immunodeficiency virus (SIV(mac)239 ) results in SIV-associated nephropathy (SIVAN) and that the glomerulo -sclerotic lesions were associated with the selection of macrophagetro pic (M-tropic) variants (V. H. Gattone et al., AIDS Res. Hum, Retrovir uses 14:1163-1180, 1998), In the present study, seven rhesus macaques were inoculated with M-tropic SIV(mac)R71/17E, and the renal pathology was examined at necropsy. All SIV(mac)R71/17E-infected macaques devel oped 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), ci rculating CD4(+) T-cell counts, and renal disease. Of the seven macaqu es inoculated with SIV(mac)R71/17E, five developed significant mesangi al hyperplasia and expansion of matrix and four were clearly azotemic (serum urea nitrogen concentration of 40 to 112 mg/dl), These same fiv e macaques developed focal segmental to global glomerulosclerotic lesi ons, Increased numbers of glomerular CD68(+) cells (monocytes/macropha ges) were found in glomeruli but not the tubulointerstitium of the mac aques inoculated with SIV(mac)R71/17E. All macaques had glomerular dep osits of immunoglobulin G (IgG), IgM, and tubuloreticular inclusions, and sis of seven had IgA deposition, However, there was no correlation between the presence of circulating anti-SIVmac antibodies, immunoglo bulin deposition, and glomerular disease. Tubulointerstitial infiltrat es were mild, with little or no correlation to azotemia, while microcy stic tubules were evident in those with glomerulosclerosis or azotemia , The four most severely affected macaques were positive for diffuse g lomerular immunostaining for viral core p27 antigen, and there was int ense staining in the glomeruli of the two macaques with the most sever e glomerulosclerosis. Viral sequences were isolated from glomerular an d tubulointerstitial fractions from macaques with severe glomeruloscle rosis but only from the tubulointerstitial compartment of those that d id not develop glomerulosclerosis, Interviral recombinant viruses gene rated with env sequences isolated from glomeruli confirmed the M-tropi c 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 g lomerular pathology confirms and extends our previous observations of an association between glomerular infection and infiltration by M-trop ic virus and SIVAN.