Type I interferons are essential in controlling neurotropic coronavirus infection irrespective of functional CD8 T cells.

Type I interferons are essential in controlling neurotropic coronavirus infection irrespective of functional CD8 T cells. Research Abstract Details 

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Type I interferons are essential in controlling neurotropic coronavirus infection irrespective of functional CD8 T cells. Abstract Text:

Derek D C Ireland,Stephen A Stohlman,David R Hinton,Roscoe Atkinson,Cornelia C Bergmann,Derek D C Ireland,Stephen A Stohlman,David R Hinton,Roscoe Atkinson,Cornelia C Bergmann,

Neurotropic coronavirus infection induces expression of both beta interferon (IFN-beta) RNA and protein in the infected rodent central nervous system (CNS). However, the relative contributions of type I IFN (IFN-I) to direct, cell-type-specific virus control or CD8 T-cell-mediated effectors in the CNS are unclear. IFN-I receptor-deficient (IFNAR(-/-)) mice infected with a sublethal and demyelinating neurotropic virus variant and those infected with a nonpathogenic neurotropic virus variant both succumbed to infection within 9 days. Compared to wild-type (wt) mice, replication was prominently increased in all glial cell types and spread to neurons, demonstrating expanded cell tropism. Furthermore, increased pathogenesis was associated with significantly enhanced accumulation of neutrophils, tumor necrosis factor alpha, interleukin-6, chemokine (C-C motif) ligand 2, and IFN-gamma within the CNS. The absence of IFN-I signaling did not impair induction or recruitment of virus-specific CD8 T cells, the primary adaptive mediators of virus clearance in wt mice. Despite similar IFN-gamma-mediated major histocompatibility complex class II upregulation on microglia in infected IFNAR(-/-) mice, class I expression was reduced compared to that on microglia in wt mice, suggesting a synergistic role of IFN-I and IFN-gamma in optimizing class I antigen presentation. These data demonstrate a critical direct antiviral role of IFN-I in controlling virus dissemination within the CNS, even in the presence of potent cellular immune responses. By limiting early viral replication and tropism, IFN-I controls the balance of viral replication and immune control in favor of CD8 T-cell-mediated protective functions.

Type I interferons are essential in controlling neurotropic coronavirus infection irrespective of functional CD8 T cells. Publishing Authors By Initials

DD Ireland,SA Stohlman,DR Hinton,R Atkinson,CC Bergmann,DD Ireland,SA Stohlman,DR Hinton,R Atkinson,CC Bergmann,

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Type I interferons are essential in controlling neurotropic coronavirus infection irrespective of functional CD8 T cells. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of virology

VOLUME: 82

Page Numbers: 300-10

Journal Abbreviation: J. Virol.

ISSN: 1098-5514

DAY: 10

MONTH: 10

YEAR: 2007

Type I interferons are essential in controlling neurotropic coronavirus infection irrespective of functional CD8 T cells. Information

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LANGUAGE: eng

NlmUniqueID: 113724

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Grant and Affiliation Information for Type I interferons are essential in controlling neurotropic coronavirus infection irrespective of functional CD8 T cells.

AFFILIATION: The Cleveland Clinic, 2500 Euclid Avenue, NC30, Cleveland, OH 44195, USA.

Country: United States

AGENCY: United States NINDS

GRANT: NS18146

ACRONYM: NS

MEDLINETA: J Virol

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