SIV-ASSOCIATED NEPHROPATHY IN RHESUS MACAQUES INFECTED WITH LYMPHOCYTE-TROPIC SIV(MAC)239

We examined the renal pathology and viral genetic changes following in oculation of six rhesus macaques with lymphocyte-tropic SIV(mac)239, P ortions of the renal cortex were sieved into glomerular and tubulointe rstitial (TI) fractions and examined for SIVmac sequences by PCR and f or p27 core antigen. SIVmac sequences were detected in renal tissue fr om 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 se quences in the glomerular fractions. Diffuse mesangial hyperplasia and matrix expansion were present in all three animals with glomerular SI V, as was an increase in glomerular collagen I and collagen IV. Tubulo interstitial inflammation was evident in all virus-inoculated macaques , The TI infiltration of CD68(+) cells was most pronounced in the anim als with SIVmac present in the glomerulus. All SIVmac-infected macaque s exhibited increased glomerular deposition of IgM and to a lesser ext ent 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 ma caque that developed glomerulopathy revealed the presence of specific viral variants in glomerular and TI fractions. In addition, chimeric v iruses constructed with glomerular but not tubulointerstitial gp120 se quences were converted to a macrophage-tropic phenotype, These results indicate that infection by lymphocyte-tropic SIV(mac)239 is primarily associated with immunoglobulin deposition in the glomerulus and sugge sts that when glomerulosclerosis develops there is selection of viral variants that are macrophage tropic in nature.