IKKε Isoform Switching Governs the Immune Response Against EV71 Infection

Overview

Journal Commun Biol

Specialty Biology

Date 2021 Jun 3

PMID 34079066

Citations 5

Authors

Ya-Ling Chang

Yu-Wen Liao

Min-Hsuan Chen

Sui-Yuan Chang

Yao-Ting Huang

Bing-Ching Ho

Sung-Liang Yu

Affiliations

Soon will be listed here.

Abstract

The reciprocal interactions between pathogens and hosts are complicated and profound. A comprehensive understanding of these interactions is essential for developing effective therapies against infectious diseases. Interferon responses induced upon virus infection are critical for establishing host antiviral innate immunity. Here, we provide a molecular mechanism wherein isoform switching of the host IKKε gene, an interferon-associated molecule, leads to alterations in IFN production during EV71 infection. We found that IKKε isoform 2 (IKKε v2) is upregulated while IKKε v1 is downregulated in EV71 infection. IKKε v2 interacts with IRF7 and promotes IRF7 activation through phosphorylation and translocation of IRF7 in the presence of ubiquitin, by which the expression of IFNβ and ISGs is elicited and virus propagation is attenuated. We also identified that IKKε v2 is activated via K63-linked ubiquitination. Our results suggest that host cells induce IKKε isoform switching and result in IFN production against EV71 infection. This finding highlights a gene regulatory mechanism in pathogen-host interactions and provides a potential strategy for establishing host first-line defense against pathogens.

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