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

研究成果: Article

20 引用 (Scopus)

抜粋

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.

元の言語English
ページ(範囲)4947-4955
ページ数9
ジャーナルJournal of Virology
86
発行部数9
DOI
出版物ステータスPublished - 2012 5
外部発表Yes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

フィンガープリント Protective role of interferon regulatory factor 3-mediated signaling against prion infection' の研究トピックを掘り下げます。これらはともに一意のフィンガープリントを構成します。

  • これを引用

    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, 86(9), 4947-4955. https://doi.org/10.1128/JVI.06326-11