Abstract:
:Reovirus infection of the murine spinal cord (SC) was used as a model system to investigate innate immune responses during viral myelitis, including the activation of glia (microglia and astrocytes) and interferon (IFN) signaling and increased expression of inflammatory mediators. Reovirus myelitis was associated with the pronounced activation of SC glia, as evidenced by characteristic changes in cellular morphology and increased expression of astrocyte and microglia-specific proteins. Expression of inflammatory mediators known to be released by activated glia, including interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α), chemokine (C-C motif) ligand 5 (CCL 5), chemokine (C-X-C motif) ligand 10 (CXCL10), and gamma interferon (IFN-γ), was also significantly upregulated in the SC of reovirus-infected animals compared to mock-infected controls. Reovirus infection of the mouse SC was also associated with increased expression of genes involved in IFN signaling, including IFN-stimulated genes (ISG). Further, reovirus infection of mice deficient in the expression of the IFN-α/β receptor (IFNAR(-/-)) resulted in accelerated mortality, demonstrating that IFN signaling is protective during reovirus myelitis. Experiments performed in ex vivo SC slice cultures (SCSC) confirmed that resident SC cells contribute to the production of at least some of these inflammatory mediators and ISG during reovirus infection. Microglia, but not astrocytes, were still activated, and glia-associated inflammatory mediators were still produced in reovirus-infected INFAR(-/-) mice, demonstrating that IFN signaling is not absolutely required for these neuroinflammatory responses. Our results suggest that activated glia and inflammatory mediators contribute to a local microenvironment that is deleterious to neuronal survival.
journal_name
J Viroljournal_title
Journal of virologyauthors
Schittone SA,Dionne KR,Tyler KL,Clarke Pdoi
10.1128/JVI.00171-12subject
Has Abstractpub_date
2012-08-01 00:00:00pages
8107-18issue
15eissn
0022-538Xissn
1098-5514pii
JVI.00171-12journal_volume
86pub_type
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journal_title:Journal of virology
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pub_type: 临床试验,杂志文章
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journal_title:Journal of virology
pub_type: 杂志文章
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更新日期:1979-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:1999-11-01 00:00:00
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