The host response to West Nile Virus infection limits viral spread through the activation of the interferon regulatory factor 3 pathway

Brenda L. Fredericksen, Maria Smith, Michael G. Katze, Pei-Yong Shi, Michael Gale

Research output: Contribution to journalArticle

111 Citations (Scopus)

Abstract

Recent outbreaks of West Nile Virus (WNV) have been associated with an increase in morbidity and mortality in humans, birds, and many other species. We have initiated studies to define the molecular mechanisms by which a recent pathogenic isolate of WNV evades the host cell innate antiviral response. Biochemical and microarray analyses demonstrated that WNV induced the expression of beta interferon (IFN-β) and several IFN-stimulated genes late in infection of cultured human cells. The late expression of these antiviral genes was due to the delayed activation of the transcription factor IFN regulatory factor 3 (IRF-3). Despite this host response, WNV was still able to replicate efficiently. The effect of the IRF-3 pathway on WNV replication was assessed by examining virus replication and spread in cultures of wild-type or IRF-3-null mouse embryo fibroblasts. The absence of IRF-3 was marked by a significant increase in plaque size and a sustained production of infectious particles. Although the activation of the IRF-3 pathway was not sufficient to block virus replication, our results suggest that IRF-3 target genes function to constrain WNV infection and limit cell-to-cell virus spread.

Original languageEnglish (US)
Pages (from-to)7737-7747
Number of pages11
JournalJournal of Virology
Volume78
Issue number14
DOIs
StatePublished - Jul 2004
Externally publishedYes

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Interferon Regulatory Factor-3
West Nile virus
Virus Diseases
Virus Replication
virus replication
infection
Antiviral Agents
cells
interferon-beta
genes
Interferon-beta
interferons
Microarray Analysis
Interferons
Genes
Birds
fibroblasts
Disease Outbreaks
morbidity
interferon regulatory factor-3

ASJC Scopus subject areas

  • Immunology

Cite this

The host response to West Nile Virus infection limits viral spread through the activation of the interferon regulatory factor 3 pathway. / Fredericksen, Brenda L.; Smith, Maria; Katze, Michael G.; Shi, Pei-Yong; Gale, Michael.

In: Journal of Virology, Vol. 78, No. 14, 07.2004, p. 7737-7747.

Research output: Contribution to journalArticle

Fredericksen, Brenda L. ; Smith, Maria ; Katze, Michael G. ; Shi, Pei-Yong ; Gale, Michael. / The host response to West Nile Virus infection limits viral spread through the activation of the interferon regulatory factor 3 pathway. In: Journal of Virology. 2004 ; Vol. 78, No. 14. pp. 7737-7747.
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