West Nile virus infection induces depletion of IFNAR1 protein levels

Jared D. Evans, Rachel A. Crown, Ji A. Sohn, Christoph Seeger

Research output: Contribution to journalArticle

Abstract

Productive virus infection requires evasion, inhibition, or subversion of innate immune responses. West Nile virus (WNV), a human pathogen that can cause symptomatic infections associated with meningitis and encephalitis, inhibits the interferon (IFN) signal transduction pathway by preventing phosphorylation of Janus kinases and STAT transcription factors. Inhibition of the IFN signal cascade abrogates activation of IFN-induced genes, thus attenuating an antiviral response. We investigated the mechanism responsible for this inhibition and found that WNV infection prevents accumulation of the IFN-α receptor subunit 1 (IFNAR1). The WNV-induced depletion of IFNAR1 was conserved across multiple cell types. Our results indicated that expression of WNV nonstructural proteins resulted in activated lysosomal and proteasomal protein degradation pathways independent of the unfolded protein response (UPR). Furthermore, WNV infection did not induce serine phosphorylation, a modification on IFNAR1 that precedes its natural turnover. These data demonstrate that WNV infection results in a reduction of IFNAR1 protein through a non-canonical protein degradation pathway, and may participate in the inhibition of the IFN response.

Original languageEnglish (US)
Pages (from-to)253-263
Number of pages11
JournalViral Immunology
Volume24
Issue number4
DOIs
StatePublished - Aug 1 2011
Externally publishedYes

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West Nile virus
Virus Diseases
Interferons
Proteins
Proteolysis
Phosphorylation
STAT Transcription Factors
Interferon Receptors
Janus Kinases
Unfolded Protein Response
Encephalitis
Meningitis
Innate Immunity
Serine
Antiviral Agents
Signal Transduction
Infection
Genes

ASJC Scopus subject areas

  • Immunology
  • Virology
  • Molecular Medicine

Cite this

Evans, J. D., Crown, R. A., Sohn, J. A., & Seeger, C. (2011). West Nile virus infection induces depletion of IFNAR1 protein levels. Viral Immunology, 24(4), 253-263. https://doi.org/10.1089/vim.2010.0126

West Nile virus infection induces depletion of IFNAR1 protein levels. / Evans, Jared D.; Crown, Rachel A.; Sohn, Ji A.; Seeger, Christoph.

In: Viral Immunology, Vol. 24, No. 4, 01.08.2011, p. 253-263.

Research output: Contribution to journalArticle

Evans, JD, Crown, RA, Sohn, JA & Seeger, C 2011, 'West Nile virus infection induces depletion of IFNAR1 protein levels', Viral Immunology, vol. 24, no. 4, pp. 253-263. https://doi.org/10.1089/vim.2010.0126
Evans, Jared D. ; Crown, Rachel A. ; Sohn, Ji A. ; Seeger, Christoph. / West Nile virus infection induces depletion of IFNAR1 protein levels. In: Viral Immunology. 2011 ; Vol. 24, No. 4. pp. 253-263.
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