Caffeic acid inhibits HCV replication via induction of IFN α antiviral response through p62-mediated Keap1/Nrf2 signaling pathway.

In this study, we showed that CA could notably inhibit HCV replication. Mechanism study demonstrated that CA could induce HO-1 expression, which would trigger the IFNα antiviral response, and the antiviral effect of CA was attenuated when HO-1 activity was inhibited by SnPP (an HO-1 inhibitor). CA could also increase erythroid 2-related factor 2 (Nrf2) expression. When Nrf2 was knocked down by specific siRNA, HO-1 expression was concomitantly decreased while HCV expression was restored. Further study indicated that kelch-like ECH-associated protein 1 (Keap1) expression was decreased by CA in a p62/Sequestosome1 (p62)-dependent way, which would lead to the stabilization and accumulation of Nrf2. The decrease of Keap1 was restored when p62 was silenced by specific p62 siRNA, suggesting p62 was required for CA-mediated Keap1 downregulation. Taken together, the results demonstrated that CA could modulate Keap1/Nrf2 interaction via increasing p62 expression, which will lead to stabilization of Nrf2 and HO-1 induction and elicit IFNα antiviral response to suppress HCV replication. PMID: 29656059 [PubMed - as supplied by publisher]
Source: Antiviral Research - Category: Virology Authors: Tags: Antiviral Res Source Type: research