Baicalin inhibits infectious bronchitis virus replication via MAVS-dependent interferon-β upregulation and mitochondrial function preservation.

The inhibitory effect of baicalin on infectious bronchitis virus (IBV) replication is closely related to expression of the mitochondrial antiviral signaling protein (MAVS) in chicken embryonic kidney (CEK) cells. Baicalin significantly upregulated MAVS expression dose-dependently and maintained mitochondrial function through MAVS. Baicalin increased expression of mitofusin-1 (Mfn1), anti-apoptotic mitochondrial import receptor subunit TOM70 (TOM70), voltage-dependent anion channel 1 (VDAC1), autophagy-related 5 (Atg5), and autophagy-related 12 (Atg12). Overexpression of Mfn1, VDAC1, TOM70, Atg5, and Atg12 enhanced baicalin-mediated interferon-β (IFN-β) expression, while knockdown of Mfn1, TOM70, VDAC1, TRADD, Atg5, or Atg12 significantly decreased IFN-β protein levels. In MAVS-knockdown cells, overexpression of Mfn1, mitofusin-2 (Mfn2), VDAC1, TNFR1-associated death domain protein (TRADD), Fas-associated death domain protein (FADD), Atg5, and Atg12 did not affect baicalin-mediated IFN-β expression. Thus, baicalin promotes mitochondrial fusion, permeability, metabolism, and autophagy. Baicalin upregulates IFN-β via Mfn1, VDAC1, TOM70, Atg5, and Atg12 dependent on MAVS. Moreover, baicalin inhibits key cytokines in the NF-κB pro-inflammatory pathway.