Protective role of interferon regulatory factor 3-mediated signaling against prion infection

Daisuke Ishibashi, Ryuichiro Atarashi, Takayuki Fuse, Takehiro Nakagaki, Naohiro Yamaguchi, Katsuya Satoh, Kenya Honda, Noriyuki Nishidaa

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Abnormal prion protein (PrPSc) generated from the cellular isoform of PrP (PrPC) is assumed to be the main or sole component of the pathogen, called prion, of transmissible spongiform encephalopathies (TSE). Because PrP is a host-encoded protein, acquired immune responses are not induced in TSE. Meanwhile, activation of the innate immune system has been suggested to partially block the progression of TSE; however, the mechanism is not well understood. To further elucidate the role of the innate immune system in prion infection, we investigated the function of interferon regulatory factor 3 (IRF3), a key transcription factor of the MyD88-independent type I interferon (IFN) production pathway. We found that IRF3-deficient mice exhibited significantly earlier onset with three murine TSE strains, namely, 22L, FK-1, and murine bovine spongiform encephalopathy (mBSE), following intraperitoneal transmission, than with wild-type controls. Moreover, overexpression of IRF3 attenuated prion infection in the cell culture system, while PrPSc was increased in prion-infected cells treated with small interfering RNAs (siRNAs) against IRF3, suggesting that IRF3 negatively regulates PrPSc formation. Our findings provide new insight into the role of the host innate immune system in the pathogenesis of prion diseases.

Original languageEnglish
Pages (from-to)4947-4955
Number of pages9
JournalJournal of Virology
Volume86
Issue number9
DOIs
Publication statusPublished - 2012 May
Externally publishedYes

Fingerprint

Interferon Regulatory Factor-3
Prion Diseases
prion diseases
Prions
prions
PrPSc proteins
Immune System
Infection
infection
mice
Bovine Spongiform Encephalopathy
Interferon Type I
bovine spongiform encephalopathy
interferons
small interfering RNA
Small Interfering RNA
Protein Isoforms
cell culture
Transcription Factors
pathogenesis

ASJC Scopus subject areas

  • Immunology
  • Virology

Cite this

Ishibashi, D., Atarashi, R., Fuse, T., Nakagaki, T., Yamaguchi, N., Satoh, K., ... Nishidaa, N. (2012). Protective role of interferon regulatory factor 3-mediated signaling against prion infection. Journal of Virology, 86(9), 4947-4955. https://doi.org/10.1128/JVI.06326-11

Protective role of interferon regulatory factor 3-mediated signaling against prion infection. / Ishibashi, Daisuke; Atarashi, Ryuichiro; Fuse, Takayuki; Nakagaki, Takehiro; Yamaguchi, Naohiro; Satoh, Katsuya; Honda, Kenya; Nishidaa, Noriyuki.

In: Journal of Virology, Vol. 86, No. 9, 05.2012, p. 4947-4955.

Research output: Contribution to journalArticle

Ishibashi, D, Atarashi, R, Fuse, T, Nakagaki, T, Yamaguchi, N, Satoh, K, Honda, K & Nishidaa, N 2012, 'Protective role of interferon regulatory factor 3-mediated signaling against prion infection', Journal of Virology, vol. 86, no. 9, pp. 4947-4955. https://doi.org/10.1128/JVI.06326-11
Ishibashi D, Atarashi R, Fuse T, Nakagaki T, Yamaguchi N, Satoh K et al. Protective role of interferon regulatory factor 3-mediated signaling against prion infection. Journal of Virology. 2012 May;86(9):4947-4955. https://doi.org/10.1128/JVI.06326-11
Ishibashi, Daisuke ; Atarashi, Ryuichiro ; Fuse, Takayuki ; Nakagaki, Takehiro ; Yamaguchi, Naohiro ; Satoh, Katsuya ; Honda, Kenya ; Nishidaa, Noriyuki. / Protective role of interferon regulatory factor 3-mediated signaling against prion infection. In: Journal of Virology. 2012 ; Vol. 86, No. 9. pp. 4947-4955.
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