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The liver is a multifunctional organ with roles in metabolism, detoxification, and the immune response. Liver secretory selenoprotein P (SeP), a hepatokine, causes insulin resistance in the liver and peripheral muscle. We showed hepatitis C virus (HCV) infection increased serum SeP levels, which may explain the increased risk of type 2 diabetes in patients with HCV infection. Increased SeP mRNA (SEPP1 mRNA) in hepatocytes inhibited type 1 interferon response by means of undefined unique mechanisms. We revealed SEPP1 mRNA directly bound to retinoic acidinducible gene I (RIG-I), a virus RNA sensor, and inhibited RIG-I activity. The robust induction of interferon-stimulated genes (>1000-fold) and repression of HCV replication (>10-fold) were observed in hepatocytes in which SEPP1 mRNA was knocked down. Clinically, high SeP serum levels were significantly associated with treatment failure of direct actingantivirals for HCV. Thus, SeP regulates insulin resistance and innate immunity, possibly inducing immune tolerance in the liver.

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.

We developed a non-radioisotopic (non-RI) reverse transcriptase assay (RTA). The reverse transcriptase (RT) incorporates biotin-11-deoxyuridine-triphosphate (bio-dUTP) using a poly(rA) template hybridized with oligo(dT) primer that is immobilized on the surface of a 96-well microtiter plate. This assay is thus semi-automated by adapting it to an ELISA testing format. The incorporation of bio-dUTP was enhanced by adding cold dTTP to the reaction mixture, optimally in a molar ratio 4:1 (dTTP:bio-dUTP). This non-RI RTA is more sensitive than the conventional RI assay for the detection of purified Rous-associated virus 2 (RAV-2) and of human immunodeficiency virus type 1 (HIV-1) lysate. Because of its simple procedure, higher sensitivity and non-use of RI materials, the assay can be utilized not only for virological studies but also for routine safety screening of biological products for retroviral contamination.

Equilibrium measurements were performed to obtain the N 2 pressure-composition isotherms at 400, 600 and 800 °C for a single-phase α-U 2 N 3+ x (0 ≦ x ≦ 1) region, using N-rich α-U 2 N 3+ x (atomic ratio N/U > 1.80) as the starting material. The equilibrium compositions of α-U 2 N 3+ x at 800 °C were also determined by equilibrating U metal with N 2 gas.