https://scholars.lib.ntu.edu.tw/handle/123456789/377240
標題: | The roles of IRF-3 and IRF-7 in innate antiviral immunity against dengue virus | 作者: | HUI-WEN CHEN King, K. Tu, J. Sanchez, M. Luster, A.D. Shresta, S. |
公開日期: | 2013 | 卷: | 191 | 期: | 8 | 起(迄)頁: | 4194-4201 | 來源出版物: | Journal of Immunology | 摘要: | We investigated the roles of IFN regulatory factor (IRF)-3 and IRF-7 in innate antiviral immunity against dengue virus (DENV). Double-deficientIrf- 3-/- 7-/- mice infected with the DENV2 strain S221 possessed 1,000-150,000 fold higher levels of viral RNA than wild-type and single-deficient mice 24 h postinfection (hpi); however, they remained resistant to lethal infection. IFN-A/bwas induced similarly in wild-type andIrf-3 -/- mice post-DENV infection, whereas in theIrf-7-/- andIrf-3-/- 7-/- mice, significantly low levels of IFN-A/bexpression was observed within 24 hpi. IFN-stimulated gene induction was also delayed inIrf-3-/- 7-/- mice relative to wild-type and single-deficient mice. In particular,Cxcl10andIfna2were rapidly induced independently of both IRF-3 and IRF-7 in theIrf-3-/- 7-/- mice with DENV infection. Higher levels of serum IFN-γ, IL-6, CXCL10, IL-8, IL-12 p70, and TNF were also observed inIrf-3-/- 7 -/- mice 24 hpi, at which time point viral titers peaked and started to be cleared. Ab-mediated blockade experiments revealed that IFN-γ, CXCL10, and CXCR3 function to restrict DENV replication in Irf-3-/- 7-/- mice. Additionally, the IFN-stimulated genesCxcl10,Ifit1,Ifit3, andMx2can be induced via an IRF-3- and IRF-7-independent pathway that does not involve IFN-γsignaling for protection against DENV. Collectively, these results demonstrate that IRF-3 and IRF-7 are redundant, albeit IRF-7 plays a more important role than IRF-3 in inducing the initial IFN-A/bresponse; only the combined actions of IRF-3 and IRF-7 are necessary for efficient control of early DENV infection; and the late, IRF-3- and IRF-7-independent pathway contributes to anti-DENV immunity. Copyright ? 2013 by The American Association of Immunologists, Inc. |
URI: | http://www.scopus.com/inward/record.url?eid=2-s2.0-84885463949&partnerID=MN8TOARS http://scholars.lib.ntu.edu.tw/handle/123456789/377240 |
DOI: | 10.4049/jimmunol.1300799 | SDG/關鍵字: | alpha interferon; alpha2 interferon; beta interferon; gamma interferon; gamma interferon inducible protein 10; interferon regulatory factor 3; interferon regulatory factor 7; interleukin 12p70; interleukin 6; interleukin 8; tumor necrosis factor; virus RNA; alpha2 interferon gene; animal experiment; animal model; animal tissue; article; controlled study; Cxc110 gene; cytokine response; dengue; gene; gene induction; infection control; innate immunity; mouse; nonhuman; priority journal; protein blood level; protein expression; protein function; virus inhibition; virus replication; virus titration; wild type; Aedes; Animals; Carrier Proteins; Cell Line; Chemokine CXCL10; Dengue; Dengue Virus; Immunity, Innate; Interferon Regulatory Factor-3; Interferon Regulatory Factor-7; Interferon-alpha; Interferon-beta; Interferon-gamma; Interleukin-12; Interleukin-6; Interleukin-8; Mice; Mice, Inbred C57BL; Mice, Knockout; Myxovirus Resistance Proteins; Proteins; Receptors, CXCR3; RNA, Viral; Signal Transduction; Tumor Necrosis Factors; Viral Load; Virus Replication |
顯示於: | 獸醫學系 |
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