International Session(Workshop)1(JSGE・JSH・JSGCS)
Thu. November 2nd   14:30 - 17:00   Room 11: Portopia Hotel South Wing Topaz
IFN-induced MxB on mitochondria inhibits HBV replication by activating a RIG-I-signaling pathway
Jun Inoue1, Masazumi Onuki1, Atsushi Masamune1
1Division of Gastroenterology, Tohoku University Graduate School of Medicine
Background/aim The role of IFN-induced myxovirus resistance protein 2 (MxB) in HBV infection is still unknown. Recently, MxB has been reported to localise to the inner membrane of mitochondria. We aimed to clarify whether MxB is involved in the innate immune response against HBV through the mitochondrial pathway.
Methods Using HBV-expressing and HBV-infected cells, the downstream signaling pathway of RIG-I was evaluated after knockdown or overexpression of MxB. Liver samples from HBV-infected patients were used for the evaluation of MxB expression.
Results Knockdown of MxB significantly increased HBsAg in the culture supernatant and envelope proteins in the HBV-expressing cells. Therefore, MxB is thought to suppress HBV replication mainly by reducing the expression of envelope proteins. When cells were stimulated with poly(I:C) and signaling downstream of RIG-I was observed, MxB knockdown inhibited the phosphorylation of TBK1 and IRF3. MAVS clustering on mitochondria is thought to be required for this pathway, but MxB knockdown inhibited MAVS clustering. MxB mRNA levels in liver samples from patients with chronic hepatitis B and acute hepatitis B were lower than in those with chronic hepatitis C. MxB mRNA levels correlated with serum albumin and platelet counts, suggesting that liver fibrosis may progress more rapidly in patients with low MxB expression.
Conclusion MxB may be required for the pathway downstream of RIG-I. Efficient induction of MxB may be an option to control HBV infection.
Index Term 1: HBV
Index Term 2: MxB
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