Related Experiment Videos
Focal segmental glomerulosclerosis in primates infected with a simian immunodeficiency virus
C E Alpers1, C C Tsai, K L Hudkins
1Department of Pathology, School of Medicine, University of Washington, Seattle 98195, USA.
Abstract:
Focal and segmental glomerulosclerosis (FSG) with endothelial tubuloreticular inclusions (TRIs) is the typical lesion of human HIV-associated glomerulopathy. Autopsy studies showed the presence of FSG in 3 of 15 macaques dying 15-120 weeks after experimental infection with a simian immunodeficiency virus (SIVMne). Ultrastructural studies generally revealed numerous endothelial TRIs (also present in normals), mesangial expansion, and evidence of mesangial cell injury. One additional animal had a small-vessel polyarteritis with a proliferative and focally crescentic glomerulonephritis; seven animals had mild, multifocal interstitial nephritis. All animals had documented viremia after infection; 14 of 15 developed antibodies to SIV postinoculation. Additional postmortem findings included severe enterocolitis, encephalitis, and opportunistic infections. In contrast, autopsy studies of macaques infected with a type D simian retrovirus (SAIDS-D/Washington, SRV-2) for similar periods of time (n = 40) showed no evidence of FSG. One SRV-infected animal had a mild proliferative glomerulonephritis. These studies indicate SIV-infected primates may provide a relevant model for study of human HIV-associated nephropathy. They also indicate the variable pathology that can be seen in primate infections of distinct retrovirus types, each of which produces a simian immunodeficiency state that resembles human AIDS.
Insights
Simian immunodeficiency virus (SIV) infection in macaques can cause focal and segmental glomerulosclerosis (FSG), a key lesion in human HIV-associated nephropathy. This finding supports SIV-infected primates as a valuable model for studying HIV kidney disease.
Area of Science:
- Nephrology
- Virology
- Pathology
Background:
- Focal and segmental glomerulosclerosis (FSG) with endothelial tubuloreticular inclusions (TRIs) characterizes human HIV-associated glomerulopathy.
- Simian immunodeficiency virus (SIV) and simian acquired immunodeficiency syndrome (SAIDS) retroviruses cause immunodeficiency in nonhuman primates.
Purpose of the Study:
- To investigate the renal pathology in macaques experimentally infected with simian immunodeficiency virus (SIVMne).
- To compare SIVMne-induced pathology with that caused by a type D simian retrovirus (SRV-2).
- To evaluate the utility of SIV-infected primates as a model for human HIV-associated nephropathy.
Main Methods:
- Autopsy and ultrastructural studies of macaques experimentally infected with SIVMne.
- Autopsy studies of macaques infected with SRV-2.
- Analysis of viremia and antibody development post-infection.
Main Results:
- FSG with endothelial TRIs was observed in 3 of 15 SIVMne-infected macaques.
- Mesangial expansion and cell injury were common in SIVMne-infected animals.
- No FSG was found in 40 SRV-2 infected macaques; one showed mild glomerulonephritis.
- SIV-infected macaques exhibited viremia and developed antibodies to SIV.
Conclusions:
- SIV-infected primates represent a relevant model for studying human HIV-associated nephropathy.
- Distinct retroviruses in primates can lead to variable pathologies, including simian immunodeficiency states resembling human AIDS.