A1 Refereed original research article in a scientific journal
Zika Virus Non-Structural Protein NS5 Inhibits the RIG-I Pathway and Interferon Lambda 1 Promoter Activation by Targeting IKK Epsilon
Authors: Lundberg R., Melén K., Westenius V., Jiang M., Österlund P., Khan H., Vapalahti O., Julkunen I., Kakkola L.
Publisher: MDPI
Publication year: 2019
Journal: Viruses
Journal name in source: VIRUSES-BASEL
Journal acronym: VIRUSES-BASEL
Article number: ARTN 1024
Volume: 11
Issue: 11
Number of pages: 20
DOI: https://doi.org/10.3390/v11111024
Web address : https://www.mdpi.com/1999-4915/11/11/1024
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/44434999
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-lambda 1 is an important antiviral molecule. In this study, we analyzed the effects of ZIKV proteins on the activation of IFN-lambda 1 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-lambda 1 promoter. Furthermore, we showed that ZIKV NS5 interacts with the protein kinase IKK epsilon, which is likely critical to the observed inhibition of phosphorylation of IRF3.
Downloadable publication This is an electronic reprint of the original article. |  |
