Induction of Selenoprotein P mRNA during Hepatitis C Virus Infection Inhibits RIG-I-Mediated Antiviral Immunity.

DEAD Box Protein 58 / antagonists & inhibitors Hepatitis C / pathology Host-Pathogen Interactions Humans Immune Evasion RNA, Messenger / metabolism Receptors, Immunologic Selenoprotein P / biosynthesis
chronic hepatitis C direct-acting antiviral drugs hepatitis C virus hepatokine innate immunity interferon retinoic-acid-inducible gene I selenoprotein P type 2 diabetes

Journal

Cell host & microbe
ISSN: 1934-6069
Titre abrégé: Cell Host Microbe
Pays: United States
ID NLM: 101302316

Informations de publication

Date de publication:
10 Apr 2019
Historique:
received: 29 05 2017
revised: 13 12 2017
accepted: 26 02 2019
entrez: 12 4 2019
pubmed: 12 4 2019
medline: 22 11 2019
Statut: ppublish

Résumé

Patients infected with hepatitis C virus (HCV) have an increased risk of developing type 2 diabetes. HCV infection is linked to various liver abnormalities, potentially contributing to this association. We show that HCV infection increases the levels of hepatic selenoprotein P (SeP) mRNA (SEPP1 mRNA) and serum SeP, a hepatokine linked to insulin resistance. SEPP1 mRNA inhibits type I interferon responses by limiting the function of retinoic-acid-inducible gene I (RIG-I), a sensor of viral RNA. SEPP1 mRNA binds directly to RIG-I and inhibits its activity. SEPP1 mRNA knockdown in hepatocytes causes a robust induction of interferon-stimulated genes and decreases HCV replication. Clinically, high SeP serum levels are significantly associated with treatment failure of direct-acting antivirals in HCV-infected patients. Thus, SeP regulates insulin resistance and innate immunity, possibly inducing immune tolerance in the liver, and its upregulation may explain the increased risk of type 2 diabetes in HCV-infected patients.

Identifiants

DOI: 10.1016/j.chom.2019.02.015 PMID: 30974086
pubmed: 30974086
pii: S1931-3128(19)30111-8
doi: 10.1016/j.chom.2019.02.015
pii:
doi:

Substances chimiques

RNA, Messenger 0
Receptors, Immunologic 0
Selenoprotein P 0
RIGI protein, human EC 3.6.1.-
DEAD Box Protein 58 EC 3.6.4.13

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

588-601.e7

Informations de copyright

Copyright © 2019 Elsevier Inc. All rights reserved.

Auteurs

Kazuhisa Murai (K)

Department of Laboratory Medicine, Kanazawa University Graduate School of Health Medicine, Kanazawa, Japan.

Masao Honda (M)

Department of Laboratory Medicine, Kanazawa University Graduate School of Health Medicine, Kanazawa, Japan; Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan. Electronic address: mhonda@m-kanazawa.jp.

Takayoshi Shirasaki (T)

Department of Laboratory Medicine, Kanazawa University Graduate School of Health Medicine, Kanazawa, Japan.

Tetsuro Shimakami (T)

Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.

Hitoshi Omura (H)

Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.

Hirofumi Misu (H)

Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.

Yuki Kita (Y)

Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.

Yumie Takeshita (Y)

Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.

Kiyo-Aki Ishii (KA)

Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.

Toshinari Takamura (T)

Department of Endocrinology and Metabolism, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.

Takeshi Urabe (T)

Public Central Hospital of Matto Ishikawa, Hakusan, Ishikawa, Japan.

Ryogo Shimizu (R)

Department of Laboratory Medicine, Kanazawa University Graduate School of Health Medicine, Kanazawa, Japan.

Hikari Okada (H)

Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.

Taro Yamashita (T)

Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.

Yoshio Sakai (Y)

Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.

Shuichi Kaneko (S)

Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.

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Classifications MeSH

questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Phosphotransferases › Nucleotidyltransferases › RNA nucleotidyltransferases › RNA helicases › DEAD-box RNA helicases › Protéine-58 à domaine DEAD › Induction of Selenoprotein P mRNA during...
questionsmedicales.fr › Maladies de l'appareil digestif › Maladies du foie › Hépatite › Hépatites virales humaines › Hépatite C › Induction of Selenoprotein P mRNA during...
questionsmedicales.fr › Phénomènes biologiques › Interactions hôte-microbes › Interactions hôte-pathogène › Induction of Selenoprotein P mRNA during...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Induction of Selenoprotein P mRNA during...
questionsmedicales.fr › Phénomènes biologiques › Interactions hôte-microbes › Interactions hôte-pathogène › Échappement immunitaire › Induction of Selenoprotein P mRNA during...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › Induction of Selenoprotein P mRNA during...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Induction of Selenoprotein P mRNA during...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Sélénoprotéines › Sélénoprotéine P › Induction of Selenoprotein P mRNA during...