ORBi: Vandevenne Patricia - The varicella-zoster virus ORF47 kinase interferes with host innate immune response by inhibiting the activation of IRF3.

Reference : The varicella-zoster virus ORF47 kinase interferes with host innate immune respons...


	Document type :	Scientific journals : Article
	Discipline(s) :	Life sciences : Biochemistry, biophysics & molecular biology
	To cite this reference:	http://hdl.handle.net/2268/103006

Title :	The varicella-zoster virus ORF47 kinase interferes with host innate immune response by inhibiting the activation of IRF3.
Language :	English
Author, co-author :	Vandevenne, Patricia [Université de Liège - ULg > Sciences de la Vie > GIGA-R, Virologie et Immunologie > >]
	Lebrun, Marielle [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Virologie et immunologie >]
	El Mjiyad, Nadia [Université de Liège - ULg > Sciences de la Vie > GIGA-R, Virologie et Immunologie > >]
	Ote, Isabelle [Université de Liège - ULg > Sciences de la Vie > GIGA-R, Virologie et Immunologie > >]
	Di Valentin, Emmanuel [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Virologie et immunologie >]
	Habraken, Yvette [Université de Liège - ULg > > GIGA-R : Virologie - Immunologie >]
	Dortu, Estelle [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques >]
	Piette, Jacques [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Virologie - Immunologie >]
	Sadzot, Catherine [Université de Liège - ULg > Département des sciences de la vie > GIGA-R : Virologie et immunologie >]
Publication date :	Feb-2011
Journal title :	PLoS ONE
Publisher :	Public Library of Science
Volume :	9
Issue/season :	2
Audience :	International
e-ISSN :	1932-6203
City :	San Franscisco
Country :	CA
Keywords :	[en] Varicella zoster virus ; Innate immunity
Abstract :	[en] The innate immune response constitutes the first line of host defence that limits viral spread and plays an important role in the activation of adaptive immune response. Viral components are recognized by specific host pathogen recognition receptors triggering the activation of IRF3. IRF3, along with NF-kappaB, is a key regulator of IFN-beta expression. Until now, the role of IRF3 in the activation of the innate immune response during Varicella-Zoster Virus (VZV) infection has been poorly studied. In this work, we demonstrated for the first time that VZV rapidly induces an atypical phosphorylation of IRF3 that is inhibitory since it prevents subsequent IRF3 homodimerization and induction of target genes. Using a mutant virus unable to express the viral kinase ORF47p, we demonstrated that (i) IRF3 slower-migrating form disappears; (ii) IRF3 is phosphorylated on serine 396 again and recovers the ability to form homodimers; (iii) amounts of IRF3 target genes such as IFN-beta and ISG15 mRNA are greater than in cells infected with the wild-type virus; and (iv) IRF3 physically interacts with ORF47p. These data led us to hypothesize that the viral kinase ORF47p is involved in the atypical phosphorylation of IRF3 during VZV infection, which prevents its homodimerization and subsequent induction of target genes such as IFN-beta and ISG15.
Research units :	Giga-Signal Transduction
Target :	Researchers
Permalink :	http://hdl.handle.net/2268/103006

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