FIG 10.

MMP-9 facilitates HBV replication by repressing IFN/JAK/STAT signaling and IFNAR1 function. We propose a novel positive-feedback regulation loop between HBV replication and MMP-9 production. Initially, HBV activates MMP-9 in infected patients and in HBV-stimulated leukocytes. Subsequently, MMP-9 facilitates HBV replication through repressing IFN/JAK/STAT signaling, interacting with IFNAR1 to block its binding with IFN-α, and promoting the phosphorylation, ubiquitination, subcellular distribution, and degradation of IFNAR1. ISRE, interferon-stimulated response element.