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Analysis of Simian Immunodeficiency Virus-specific CD8+ T-cells in Rhesus Macaques by Peptide-MHC-I Tetramer Staining
Published on: December 23, 2016
Atypical nodular astrocytosis in simian immunodeficiency virus-infected rhesus macaques (Macaca mulatta)
Keiko Y Petrosky1, Heather L Knight, Susan V Westmoreland
1Division of Comparative Pathology, New England Primate Research Center, Harvard Medical School, Southborough, MA, USA.
Background:
Simian immunodeficiency virus (SIV), a model for HIV pathogenesis, is associated with neuropathology.
Methods:
Five SIV-infected animals were selected following a database search of 1206 SIV-infected animals for nodular or astrocytic lesions. Two of five had neurologic dysfunction, and 3 of 5 were incidental findings.
Results:
Histologic examination revealed multifocal nodular foci in the gray and white matter formed by interlacing astrocytes with abundant cytoplasm and large, reactive nuclei. Nodules were often enmeshed with small capillaries. Immunohistochemistry revealed variable immunoreactivity for a panel of markers: GFAP (4/5), vimentin (5/5), Glut-1 (1/5), CNPase (0/5), S100 (5/5), Iba1 (0/5), Ki67 (0/5), and p53 (4/4). In situ hybridization failed to detect any SIV RNA (0/5). Immunohistochemistry for simian virus 40, rhesus cytomegalovirus, and rhesus lymphocryptovirus failed to detect any antigen within the lesions.
Conclusion:
The immunoreactivity of p53 in the lesions compared with adjacent tissue suggests a local derangement in astrocyte proliferation and function.
Insights
Simian immunodeficiency virus (SIV) infection in macaques causes unique astrocyte lesions in the brain. These lesions show altered astrocyte proliferation and function, but without detectable SIV RNA.
Area of Science:
- Neuroscience
- Virology
- Pathology
Background:
- Simian immunodeficiency virus (SIV) infection serves as a model for human immunodeficiency virus (HIV) pathogenesis.
- SIV infection is frequently associated with neuropathology.
Observation:
- Histologic examination of SIV-infected animals revealed multifocal nodular lesions in gray and white matter.
- These lesions were characterized by interlacing astrocytes with abundant cytoplasm and reactive nuclei, often associated with small capillaries.
Findings:
- Immunohistochemistry showed variable reactivity for GFAP, vimentin, and S100 in the lesions.
- Importantly, p53 immunoreactivity was detected in lesions, suggesting a derangement in astrocyte proliferation and function.
- No SIV RNA or antigens from common simian viruses were detected within the lesions.
Implications:
- The findings suggest that SIV-induced neuropathology involves specific astrocyte abnormalities.
- Further research is needed to elucidate the mechanisms driving these astrocyte changes in SIV infection.
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