Progressive cytomegalovirus glomerulonephritis - An experimental model.
Although acute infection with murine cytomegalovirus (MCMV) resulted in a transient focal glomerulonephritis characterized by mesangial inclusions, infection of HA/ICR mice given antilymphocyte globulin (ALG) led to progressive glomerulonephritis and renal failure. ALG alone without virus failed to produce progressive renal disease. Mice given both MCMV and ALG developed severe proteinuria and azotemia with glomerular crescents by 30 days. By immunofluorescence, viral antigen was limited to mesangial zones and glomerular axial poles. Granular deposits of rabbit IgG from ALG, mouse IgG, and C3 along the peripheral glomerular capillary walls were first observed 12 days after infection. By electron microscopy, virus was found only in glomerular mesangial cells that resembled macrophages. Intramembranous and subepithelial deposits in peripheral capillary walls were associated with accumulations of polymorphonuclear leukocytes dissecting into glomerular basement membranes. These observations best fit a multiphasic mechanism of glomerular injury initiated by persistent virus in the mesangium, followed by deposits of rabbit IgG from ALG, mouse IgG, and C in the peripheral capillary walls, resulting in an amplified immune-complex-mediated injury. Because other viruses localize within the glomerular mesangium, viruses should be considered potential causes of mesangial injury and progressive glomerulonephritis.
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D000961:Antilymphocyte Serum / Q000008:administration & dosage; D001806:Blood Urea Nitrogen; D003176:Complement C3 / Q000032:analysis; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D005337:Fibrin / Q000032:analysis; D005921:Glomerulonephritis / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D007074:Immunoglobulin G / Q000032:analysis; D007677:Kidney Function Tests; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D051379:Mice; D008813:Mice, Inbred ICR; D011507:Proteinuria / Q000209:etiology; D011817:Rabbits
D000956:Antigens, Viral; D000961:Antilymphocyte Serum; D003176:Complement C3; D007074:Immunoglobulin G; D005337:Fibrin