MicroRNA-130a can inhibit hepatitis B virus replication via targeting PGC1α and PPARγ

In hepatitis B virus (HBV)-replicating hepatocytes, miR-130a expression was significantly reduced. In a reciprocal manner, miR-130a reduced HBV replication by targeting at two major metabolic regulators PGC1 alpha and PPAR gamma, both of which can potently stimulate HBV replication. We proposed a positive feed-forward loop between HBV, miR-130a, PPAR gamma, and PGC1 alpha. Accordingly, HBV can significantly enhance viral replication by reducing miR-130a and increasing PGC1a and PPAR gamma NF-kappa B/p65 can strongly stimulate miR-130a promoter, while miR-130a can promote NF-kappa B/p65 protein level by reducing PPAR gamma and thus NF-kappa B/p65 protein degradation. We postulated another positive feed-forward loop between miR-130a and NF-kappa B/p65 via PPAR gamma. During liver inflammation, NF-kappa B signaling could contribute to viral clearance via its positive effect on miR-130a transcription. Conversely, in asymptomatic HBV carriers, persistent viral infection could reduce miR-130a and NF-kappa B expression, leading to dampened inflammation and immune tolerance. Finally, miR-130a could contribute to metabolic homeostasis by dual targeting PGC1 alpha and PPAR gamma simultaneously.