[PDF][PDF] Induction of selenoprotein P mRNA during hepatitis C virus infection inhibits RIG-I-mediated antiviral immunity

K Murai, M Honda, T Shirasaki, T Shimakami… - Cell host & …, 2019 - cell.com
K Murai, M Honda, T Shirasaki, T Shimakami, H Omura, H Misu, Y Kita, Y Takeshita, K Ishii
Cell host & microbe, 2019cell.com
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 …
Summary
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.
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