| Literature DB >> 30974086 |
Kazuhisa Murai1, Masao Honda2, Takayoshi Shirasaki1, Tetsuro Shimakami3, Hitoshi Omura3, Hirofumi Misu4, Yuki Kita4, Yumie Takeshita4, Kiyo-Aki Ishii4, Toshinari Takamura4, Takeshi Urabe5, Ryogo Shimizu1, Hikari Okada3, Taro Yamashita3, Yoshio Sakai3, Shuichi Kaneko3.
Abstract
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.Entities:
Keywords: chronic hepatitis C; direct-acting antiviral drugs; hepatitis C virus; hepatokine; innate immunity; interferon; retinoic-acid-inducible gene I; selenoprotein P; type 2 diabetes
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Year: 2019 PMID： 30974086 DOI： 10.1016/j.chom.2019.02.015
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 21.023