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SIV-associated nephropathy in rhesus macaques infected with lymphocyte-tropic SIVmac239
1Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City 66160, USA.
Abstract:
We examined the renal pathology and viral genetic changes following inoculation of six rhesus macaques with lymphocyte-tropic SIVmac239. Portions of the renal cortex were sieved into glomerular and tubulointerstitial (TI) fractions and examined for SIVmac sequences by PCR and for p27 core antigen. SIVmac sequences were detected in renal tissue from 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 sequences in the glomerular fractions. Diffuse mesangial hyperplasia and matrix expansion were present in all three animals with glomerular SIV, as was an increase in glomerular collagen I and collagen IV. Tubulointerstitial inflammation was evident in all virus-inoculated macaques. The TI infiltration of CD68+ cells was most pronounced in the animals with SIVmac present in the glomerulus. All SIVmac-infected macaques exhibited increased glomerular deposition of IgM and to a lesser extent 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 macaque that developed glomerulopathy revealed the presence of specific viral variants in glomerular and TI fractions. In addition, chimeric viruses constructed with glomerular but not tubulointerstitial gp120 sequences were converted to a macrophage-tropic phenotype. These results indicate that infection by lymphocyte-tropic SIVmac239 is primarily associated with immunoglobulin deposition in the glomerulus and suggests that when glomerulosclerosis develops there is selection of viral variants that are macrophage tropic in nature.
Insights
Simian immunodeficiency virus (SIVmac239) infection in macaques can cause kidney damage, including glomerulosclerosis. Specific viral variants selected in the kidneys may become macrophage-tropic, contributing to disease progression.
Area of Science:
- Nephrology
- Virology
- Immunology
Background:
- Lymphocyte-tropic SIVmac239 infection in rhesus macaques can lead to renal pathology.
- Understanding the interplay between viral genetics and kidney disease is crucial for developing effective treatments.
Purpose of the Study:
- To investigate renal pathology and viral genetic changes in macaques infected with SIVmac239.
- To determine if specific viral variants are selected in the kidney and if they exhibit altered tropism.
Main Methods:
- Rhesus macaques were inoculated with SIVmac239.
- Renal cortex was fractionated into glomerular and tubulointerstitial (TI) components.
- SIVmac sequences and p27 core antigen were detected using PCR and immunoassay.
- Glomerular and TI viral env gene (gp120) sequences were analyzed.
- Chimeric viruses were constructed to assess tropism.
Main Results:
- SIVmac sequences were detected in renal tissues of most infected macaques.
- Glomerulosclerosis, mesangial hyperplasia, and increased collagen deposition were observed in macaques with glomerular SIV.
- Tubulointerstitial inflammation and CD68+ cell infiltration were present in all infected animals.
- Immunoglobulin (IgM, IgG) deposition was increased in glomeruli.
- Glomerular SIV env sequences from a glomerulopathy case yielded macrophage-tropic chimeric viruses.
Conclusions:
- SIVmac239 infection is associated with immunoglobulin deposition in the glomerulus.
- Glomerulosclerosis development correlates with the selection of macrophage-tropic viral variants.
- Kidney infection can drive viral evolution towards macrophage tropism.