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Título : The ebola virus protein vp35, impairs the function of the 2 3 interferon regulatory factor-activating kinases, ikkε and tbk-1
Autor : Cardenas Medranda, Washington Bolívar
Palabras clave : EBOLA VIRUS PROTEIN VP35
Fecha de publicación : 2009
Resumen : The Ebola virus (EBOV) VP35 protein antagonizes the early, antiviral interferon (IFN) α/β response. We previously demonstrated that VP35 inhibits virus-induced activation of the IFN β promoter by blocking the phosphorylation of interferon-regulatory factor 3 (IRF-3), a transcription factor crucial for the induction of IFN α/β expression. Further, VP35 blocks IFN β promoter activation induced by any of several components of the retinoic acid-inducible gene I (RIG-I)/melanoma differentiation-associated gene 5 (MDA-5) activated signaling pathways including: RIG-I, interferon-beta promoter stimulator-1 (IPS-1), TANK-binding kinase-1 (TBK- 1) and IκB kinase epsilon (IKKε). These results suggested that VP35 may target the IRF kinases, TBK-1 and ΙΚΚε. Co-immunoprecipitation experiments now demonstrate physical interaction of VP35 with IΚΚε and TBK-1, and use of an ΙΚΚε deletion construct further demonstrates that the amino termina kinase domain of ΙΚΚε is sufficient for interaction with either IRF-3 or VP35. In vitro, either ΙΚΚε or TBK-1 phosphorylate not only IRF-3 but also VP35. Moreover VP35 over-expression impairs ΙΚΚε-IRF-3, ΙΚΚε-IRF-7, and ΙΚΚε-IPS-1 interactions. Finally, lysates from cells over-expressing IKKε contain kinase activity that can phosphorylate IRF-3 in vitro. When VP35 is expressed in the IKKε-expressing cells, this kinase activity is suppressed. These data suggest that VP35 exerts its IFN-antagonist function, at least in part, by blocking necessary interactions between the kinases, ΙΚΚε/TBK-1, and their normal interaction partners, including their substrates, IRF-3 and IRF-7.
URI : http://www.dspace.espol.edu.ec/handle/123456789/5866
Aparece en las colecciones: Laboratorio Biomedicina - FIMCBOR

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