Article (Scientific journals)
The varicella-zoster virus ORF47 kinase interferes with host innate immune response by inhibiting the activation of IRF3.
Vandevenne, Patricia; Lebrun, Marielle; El Mjiyad, Nadia et al.
2011In PLoS ONE, 9 (2)
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Keywords :
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 center :
Giga-Signal Transduction - ULiège
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Vandevenne, Patricia ;  Université de Liège - ULiège > Sciences de la Vie > GIGA-R, Virologie et Immunologie
Lebrun, Marielle  ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie et immunologie
El Mjiyad, Nadia;  Université de Liège - ULiège > Sciences de la Vie > GIGA-R, Virologie et Immunologie
Ote, Isabelle;  Université de Liège - ULiège > Sciences de la Vie > GIGA-R, Virologie et Immunologie
Di Valentin, Emmanuel  ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie et immunologie
Habraken, Yvette ;  Université de Liège - ULiège > GIGA-R : Virologie - Immunologie
Dortu, Estelle ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Anatomie et cytologie pathologiques
Piette, Jacques ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie - Immunologie
Sadzot-Delvaux, Catherine ;  Université de Liège - ULiège > Département des sciences de la vie > GIGA-R : Virologie et immunologie
Language :
English
Title :
The varicella-zoster virus ORF47 kinase interferes with host innate immune response by inhibiting the activation of IRF3.
Publication date :
February 2011
Journal title :
PLoS ONE
eISSN :
1932-6203
Publisher :
Public Library of Science, San Franscisco, United States - California
Volume :
9
Issue :
2
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 14 November 2011

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