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Association of simian virus 40 with a central nervous system lesion distinct from progressive multifocal
M A Simon1, P O Ilyinskii, G B Baskin
1Division of Comparative Pathology, New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772-9102, USA. meredith_simon@hms.harvard.edu
Abstract:
The primate polyomavirus SV40 is known to cause interstitial nephritis in primary infections and progressive multifocal leukoencephalopathy (PML) upon reactivation of a latent infection in SIV-infected macaques. We now describe a second central nervous system manifestation of SV40: a meningoencephalitis affecting cerebral gray matter, without demyelination, distinct from PML. Meningoencephalitis appears also to be a primary manifestation of SV40 infection and can be seen in conjunction with SV40-induced interstitial nephritis and pneumonitis. The difference in the lesions of meningoencephalitis and PML does not appear to be due to cellular tropism, as both oligodendrocytes and astrocytes are infected in PML and meningoencephalitis, as determined by in situ hybridization or immunohistochemistry for SV40 coupled with immunohistochemistry for cellular determinants. This is further supported by examination of SV40 nucleic acid sequences from the ori-enhancer and large-T-antigen regions, which reveals no tissue-or lesion-specific variation in SV40 sequences.
Insights
Simian virus 40 (SV40) causes a distinct meningoencephalitis in the central nervous system, separate from progressive multifocal leukoencephalopathy (PML). This new finding reveals another primary manifestation of SV40 infection in primates.
Area of Science:
- Virology
- Neuropathology
- Primate Immunology
Background:
- Simian virus 40 (SV40) is a primate polyomavirus.
- SV40 is known to cause interstitial nephritis and, upon reactivation, progressive multifocal leukoencephalopathy (PML) in SIV-infected macaques.
Purpose of the Study:
- To describe a novel central nervous system manifestation of SV40 infection.
- To differentiate this new condition from SV40-induced PML.
Main Methods:
- In situ hybridization and immunohistochemistry were used to detect SV40 in infected tissues.
- SV40 nucleic acid sequences were analyzed from the ori-enhancer and large-T-antigen regions.
Main Results:
- A distinct meningoencephalitis affecting cerebral gray matter, without demyelination, was identified as a second central nervous system manifestation of SV40.
- This meningoencephalitis appears to be a primary infection, potentially co-occurring with interstitial nephritis and pneumonitis.
- Both oligodendrocytes and astrocytes were infected in both PML and meningoencephalitis lesions, indicating no difference in cellular tropism.
- SV40 sequences showed no tissue- or lesion-specific variations.
Conclusions:
- SV40 can cause meningoencephalitis as a primary manifestation, distinct from PML.
- The pathogenesis of SV40-induced neurological disease does not appear to be related to variations in viral sequences or cellular tropism.