Residues Asn118 and Glu119 of hepatitis B virus X protein are critical for HBx-mediated inhibition of RIG-I-MAVS signaling

Abstract

Hepatitis B virus (HBV) X protein (HBx) has been reported to counteract the innate immune responses through interfering with the pattern recognition receptors signaling activated by retinoic acid-inducible gene-I (RIG-I)-mitochondrial antiviral signaling protein (MAVS). Here, we showed that, compared to the HBx derived from genotype (gt) A, C and D, HBx of gtB exhibited more potent inhibitory activity on the RIG-I-MAVS-mediated interferon-β promoter activation. Functional analysis of the genotype-associated differences in amino acid sequence and the reciprocal mutation experiments in transient-transfection and infection cell models revealed that HBx with asparagine (N) and glutamic acid (E) at 118–119 positions inhibited RIG-I signaling and interacted with MAVS more efficiently than that with lysine (K) and aspartic acid (D). An impaired RIG-I-induced MAVS aggregation was observed in the presence of HBx-118N119E while MAVS-TRAF3 interaction was not affected. These results implicated that HBx gene heterogeneity may affect the innate immune responses to HBV infection.