Murine retrovirus-induced spongiform encephalopathy: disease expression is dependent on postnatal development of the central nervous system.
AUTOR(ES)
Lynch, W P
RESUMO
In this report, we have examined the role of central nervous system (CNS) development in the pathogenesis of neurodegenerative disease induced by murine retroviruses. This was accomplished by comparing the effect of delivering viruses, with either severe or marginal neurovirulence (J. L. Portis, S. Czub, C. F. Garon, and F. J. McAtee, J. Virol. 64:1648-1656, 1990), during the midgestational development of the mouse (gestation days 9 to 10). Midgestation inoculation of the marginally neurovirulent virus, 15-1, resulted in high level CNS infection, as determined by viral DNA and protein analysis. The high-level infection resulted in rapid, severe disease with 100% incidence and an average clinical onset on postnatal day 17 (P17). The disease onset was comparable to that observed for the highly neurovirulent virus, FrCasE, when inoculated neonatally (onset ca. P16). To evaluate whether disease could be induced even earlier in CNS development, FrCasE was inoculated during midgestation. Surprisingly, neither clinical nor histological manifestations of CNS disease were accelerated but rather appeared at the same developmental time as seen for neonatally inoculated animals (onset of neuropathology at ca. P10; onset of clinical disease at ca. P15). CNS infection, on the other hand, occurred at earlier times (< P0), at higher levels, and with a broader distribution than in neonatally inoculated animals. No infection of the neurons which ultimately degenerate was observed in any regimen of virus inoculation. It was observed, however, that the gp70 viral envelope protein from the CNS showed an increase mobility on sodium dodecyl sulfate-polyacrylamide gel electrophoresis compared with the envelope protein from infected spleens or purified virions. These results indicate that a postnatal developmental event must occur to allow the presence of a neurovirulent virus to precipitate spongiform degeneration and that an altered envelope protein may be participating in the process.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=237581Documentos Relacionados
- Age-dependent resistance to murine retrovirus-induced spongiform neurodegeneration results from central nervous system-specific restriction of virus replication.
- Retrovirus-induced spongiform encephalopathy: the 3'-end long terminal repeat-containing viral sequences influence the incidence of the disease and the specificity of the neurological syndrome.
- Retrovirus-induced murine motor neuron disease: mapping the determinant of spongiform degeneration within the envelope gene.
- Endoplasmic Reticulum Stress Is a Determinant of Retrovirus-Induced Spongiform Neurodegeneration
- Murine retrovirus-induced spongiform encephalomyelopathy: host and viral factors which determine the length of the incubation period.