Early expression of IFN-α/β and iNOS in the brains of venezuelan equine encephalitis virus-infected mice

Bruce Schoneboom, James S. Lee, Franziska B. Grieder

Research output: Contribution to journalArticle

Abstract

To investigate the roles of type I interferon (IFN-α/β) and other mediators of innate immune responses (e.g., inducible nitric oxide synthase [iNOS]) in early dissemination of Venezuelan equine encephalitis virus (VEE) infection, we used mice with targeted deletions in either their IFN-α/β- receptor (IFNAR-1(-/-)) or interferon regulatory factor 2 (IRF-2(-/-)) genes. Following footpad infection, both IFNAR-1(-/-) and IRF-2(-/-) mice were more susceptible than control mice to VEE. The IFNAR-1(-/-) mice also exhibit accelerated VEE dissemination to serum, spleen, and brain, and compared with control mice, they evidenced faster kinetics in the upregulation of proinflammatory genes. In contrast, in IRF-2(-/-) mice, iNOS gene induction was completely absent following peripheral virulent VEE infection. In evaluating the role of cells involved in iNOS production, primary microglial cell cultures were found to be highly permissive to VEE infection. Moreover, VEE infection increased levels of nitric oxide (NO) in resting microglial cultures but decreased NO production in IFNγ-stimulated microglia. Thus, these findings suggest that reactive nitrogen species play an important contributory role in VEE dissemination and survival of the host. Our results further suggest the necessity for a carefully balanced host response that follows a middle course between immunopathology and insufficient inflammatory response to VEE infection.

Original languageEnglish (US)
Pages (from-to)205-215
Number of pages11
JournalJournal of Interferon and Cytokine Research
Volume20
Issue number2
DOIs
StatePublished - Mar 11 2000
Externally publishedYes

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Venezuelan Equine Encephalitis Viruses
Nitric Oxide Synthase Type II
Interferons
Virus Diseases
Brain
Interferon Regulatory Factor-2
Nitric Oxide
Interferon Receptors
Genes
Reactive Nitrogen Species
Interferon Type I
Primary Cell Culture
Microglia
Innate Immunity
Up-Regulation
Spleen
Infectious Encephalitis

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

Cite this

Early expression of IFN-α/β and iNOS in the brains of venezuelan equine encephalitis virus-infected mice. / Schoneboom, Bruce; Lee, James S.; Grieder, Franziska B.

In: Journal of Interferon and Cytokine Research, Vol. 20, No. 2, 11.03.2000, p. 205-215.

Research output: Contribution to journalArticle

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