Epstein-Barr virus (EBV)-encoded small RNA is released from EBV-infected cells and activates signaling from toll-like receptor 3
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概要
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Epstein-Barr virus-encoded small RNA (EBER) is nonpolyadenylated, noncoding RNA that forms stem-loop structure by intermolecular base-pairing, giving rise to double-stranded RNA (dsRNA)-like molecules, and exists abundantly in EBV-infected cells. Here, we report that EBER induces signaling from the Toll-like receptor 3 (TLR3), which is a sensor of viral double-stranded RNA (dsRNA) and induces type I IFN and proinflammatory cytokines. A substantial amount of EBER, which was sufficient to induce signaling from TLR3, was released from EBV-infected cells, and the majority of the released EBER existed as a complex with a cellular EBER-binding protein La, suggesting that EBER was released from the cells by active secretion of La. Sera from patients with infectious mononucleosis (IM), chronic active EBV infection (CAEBV), and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), whose general symptoms are caused by proinflammatory cytokines contained EBER, and addition of RNA purified from the sera into culture medium induced signaling from TLR3 in EBV-transformed lymphocytes and peripheral mononuclear cells. Furthermore, DCs treated with EBER showed mature phenotype and antigen presentation capacity. These findings suggest that EBER, which is released from EBV-infected cells, is responsible for immune activation by EBV, inducing type I IFN and proinflammatory cytokines. EBER-induced activation of innate immunity would account for immunopathologic diseases caused by active EBV infection.
- Rockefeller University Pressの論文
- 2009-09-28
著者
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Ebihara Takashi
北海道大学 医学研究科免疫学
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Matsumoto Misako
北海道大学 医学研究科免疫学
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Matsumoto M
Department Of Microbiology And Immunology Hokkaido University Graduate School Of Medicine
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Seya Tsukasa
大阪府立成人病センター研究所 免疫学部門
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Seya Tsukasa
北海道大学 医学研究科免疫学
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Seya Tsukasa
Department Of Immunology Osaka Medical Center For Cancer And Cardiovascular Diseases:probrain
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Ebihara Takashi
Department Of Microbiology And Immunology Hokkaido University Graduate School Of Medicine
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松本 美佐子
Department Of Microbiology And Immunology Hokkaido University Graduate School Of Medicine
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Seto Toshiyuki
Daparment Of Virology
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Matsumoto Masanori
Laboratory Of Immunodynamics Department Of Microbiology And Immunology Osaka University Graduate Sch
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