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Open AccessArticle

Zika Virus Non-Structural Protein NS5 Inhibits the RIG-I Pathway and Interferon Lambda 1 Promoter Activation by Targeting IKK Epsilon

1
Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, 20520 Turku, Finland
2
Expert Microbiology Unit, National Institute for Health and Welfare, Mannerheimintie 166, 00300 Helsinki, Finland
3
Department of Virology, University of Helsinki, Haartmaninkatu 3, 00290 Helsinki, Finland
4
Turku University Central Hospital, Clinical microbiology, Kiinamyllynkatu 10, 20520 Turku, Finland
*
Author to whom correspondence should be addressed.
Viruses 2019, 11(11), 1024; https://doi.org/10.3390/v11111024
Received: 22 October 2019 / Accepted: 1 November 2019 / Published: 4 November 2019
(This article belongs to the Section Animal Viruses)
The Zika virus (ZIKV) is a member of the Flaviviridae family and an important human pathogen. Most pathogenic viruses encode proteins that interfere with the activation of host innate immune responses. Like other flaviviruses, ZIKV interferes with the expression of interferon (IFN) genes and inhibits IFN-induced antiviral responses. ZIKV infects through epithelial barriers where IFN-λ1 is an important antiviral molecule. In this study, we analyzed the effects of ZIKV proteins on the activation of IFN-λ1 promoter. All ZIKV proteins were cloned and transiently expressed. ZIKV NS5, but no other ZIKV protein, was able to interfere with the RIG-I signaling pathway. This inhibition took place upstream of interferon regulatory factor 3 (IRF3) resulting in reduced phosphorylation of IRF3 and reduced activation of IFN-λ1 promoter. Furthermore, we showed that ZIKV NS5 interacts with the protein kinase IKKε, which is likely critical to the observed inhibition of phosphorylation of IRF3.
Keywords: Zika virus; innate immunity; interferon; IKK epsilon Zika virus; innate immunity; interferon; IKK epsilon
MDPI and ACS Style

Lundberg, R.; Melén, K.; Westenius, V.; Jiang, M.; Österlund, P.; Khan, H.; Vapalahti, O.; Julkunen, I.; Kakkola, L. Zika Virus Non-Structural Protein NS5 Inhibits the RIG-I Pathway and Interferon Lambda 1 Promoter Activation by Targeting IKK Epsilon. Viruses 2019, 11, 1024.

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