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J Microbiol Biotechnol. 2018 Sep 28;28(9):1554-1562. doi: 10.4014/jmb.1808.08058.

Hepatitis E Virus Methyltransferase Inhibits Type I Interferon Induction by Targeting RIG-I.

Author information

1
Korea Zoonosis Research Institute and Genetic Engineering Research Institute, Chonbuk National University, Jeonju 54896, Republic of Korea.
2
Department of Food and Nutrition, Chung-Ang University, Anseong 17546, Republic of Korea.
3
Department of Infectious Disease, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.
4
Biological Disaster Analysis Group, Korea Basic Science Research Institute, Daejeon 34133, Republic of Korea.
5
World Institute of Kimchi, Gwangju 61755, Republic of Korea.
6
Food and Bio-industry Research Institute, Kyungpook National University, Daegu 41566, Republic of Korea.
7
Center for Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon 34114, Republic of Korea.

Abstract

The type I interferons (IFNs) play a vital role in activation of innate immunity in response to viral infection. Accordingly, viruses have evolved to employ various survival strategies to evade innate immune responses induced by type I IFNs. For example, HEV encoded papainlike cysteine protease (PCP) has been shown to inhibit IFN activation signaling by suppressing K63-linked de-ubiquitination of retinoic acid-inducible gene I (RIG-I) and TANK-binding kinase 1 (TBK1), thus effectively inhibiting down-stream activation of IFN signaling. In present study, we demonstrated that hepatitis E virus (HEV) inhibits poly inosinicpolycytidylic acid (poly(I:C))-induced IFN-β transcriptional induction. Moreover, by using reporter assay with individual HEV-encoded gene, we showed that HEV methyltransferase (MeT), a non-structural protein, significantly decreases RIG-I-induced IFN-β induction and NF-κB signaling activities in a dose-dependent manner. Taken together, we report here that MeT, along with PCP, is responsible for the inhibition of RIG-I-induced activation of type I IFNs, expanding the list of HEV-encoded antagonists of the host innate immunity.

KEYWORDS:

Hepatitis E virus; RIG-I; methyltransferase

PMID:
30199924
DOI:
10.4014/jmb.1808.08058
[Indexed for MEDLINE]
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