tetano
Editor, Senior Moderator
J Virol. 2014 May 7. [Epub ahead of print]
RIOK3 is an adaptor protein required for IRF3-mediated antiviral type I interferon production.
Feng J1, De Jesus PD, Su V, Han S, Gong D, Wu NC, Tian Y, Li X, Wu TT, Chanda SK, Sun R.
Author information
Abstract
Detection of cytosolic nucleic acids by pattern recognition receptors leads to the induction of type I interferons and elicits the innate immune response. Here we report the identification of RIOK3 as a novel adaptor protein that is essential for the cytosolic nucleic acid induced type I IFN production and for antiviral response to gammaherpesvirus through two independent kinome-wide RNAi screens. RIOK3 knockdown blocks both cytosolic BDNA and dsRNA induced IRF3 activation and IFNβ production. In contrast, overexpression of RIOK3 activates IRF3 and induces IFNβ. RIOK3 functions downstream of TBK1 and upstream of IRF3 activation. Furthermore, RIOK3 physically interacts with both IRF3 and TBK1, and is necessary for the interaction between TBK1 and IRF3. In addition, global transcriptome analysis shows that the expression of many gene involved antiviral responses is dependent on RIOK3. Thus, knockdown of RIOK3 inhibits cellular antiviral responses against both DNA and RNA viruses (herpesvirus and influenza A virus). Our data suggests that RIOK3 plays a critical role in the antiviral type I interferon pathway by bridging TBK1 and IRF3.
IMPORTANCE:
The innate immune response, such as production of type I interferons, acts as the first line of defense, limiting infectious pathogens directly and shaping the adaptive immune response. In this study, we identified RIOK3 as a novel regulator of the antiviral type I interferon pathway. Specifically, we found that RIOK3 physically interacts with TBK1 and IRF3 and bridges the functions between TBK1 and IRF3 in the activation of type I interferon pathway. The identification of a cellular kinase that plays a role the type I interferon pathway adds another level of complexity in the regulation of innate immunity and will have implications for developing novel strategies to combat viral infection.
PMID:
24807708
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24807708
RIOK3 is an adaptor protein required for IRF3-mediated antiviral type I interferon production.
Feng J1, De Jesus PD, Su V, Han S, Gong D, Wu NC, Tian Y, Li X, Wu TT, Chanda SK, Sun R.
Author information
Abstract
Detection of cytosolic nucleic acids by pattern recognition receptors leads to the induction of type I interferons and elicits the innate immune response. Here we report the identification of RIOK3 as a novel adaptor protein that is essential for the cytosolic nucleic acid induced type I IFN production and for antiviral response to gammaherpesvirus through two independent kinome-wide RNAi screens. RIOK3 knockdown blocks both cytosolic BDNA and dsRNA induced IRF3 activation and IFNβ production. In contrast, overexpression of RIOK3 activates IRF3 and induces IFNβ. RIOK3 functions downstream of TBK1 and upstream of IRF3 activation. Furthermore, RIOK3 physically interacts with both IRF3 and TBK1, and is necessary for the interaction between TBK1 and IRF3. In addition, global transcriptome analysis shows that the expression of many gene involved antiviral responses is dependent on RIOK3. Thus, knockdown of RIOK3 inhibits cellular antiviral responses against both DNA and RNA viruses (herpesvirus and influenza A virus). Our data suggests that RIOK3 plays a critical role in the antiviral type I interferon pathway by bridging TBK1 and IRF3.
IMPORTANCE:
The innate immune response, such as production of type I interferons, acts as the first line of defense, limiting infectious pathogens directly and shaping the adaptive immune response. In this study, we identified RIOK3 as a novel regulator of the antiviral type I interferon pathway. Specifically, we found that RIOK3 physically interacts with TBK1 and IRF3 and bridges the functions between TBK1 and IRF3 in the activation of type I interferon pathway. The identification of a cellular kinase that plays a role the type I interferon pathway adds another level of complexity in the regulation of innate immunity and will have implications for developing novel strategies to combat viral infection.
PMID:
24807708
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24807708