Myricetin activates innate antiviral immunity during PRRSV infection in MARC-145 cells

Porcine reproductive and respiratory syndrome virus (PRRSV) continues to impose a severe economic burden on the global swine industry, primarily due to its profound ability to evade host innate immune surveillance, particularly by suppressing type I and II interferon (IFN) signaling. Therefore, there is an urgent need to develop an effective strategy for the prevention and treatment of PRRSV. Myricetin, a natural flavonol with potent antiviral and anti-inflammatory properties, has emerged as a highly promising broad-spectrum antiviral agent. In this study, we systematically evaluated the immunomodulatory and antiviral efficacies of myricetin against PRRSV infection in MARC-145 cells. Results showed a favorable safety profile, with cell viability above 95% at concentrations up to 250 μM. Furthermore, myricetin inhibited PRRSV replication in a dose- and time-dependent manner. Treatment with 250 μM myricetin drastically reduced viral RNA levels by approximately 4.7 log units (>50,000-fold) and decreased infectious progeny titers by over 3 log units. Notably, PRRSV infection alone failed to trigger significant interferon secretion; however, under myricetin treatment, the expression of IFN-α, IFN-β, and IFN-γ at both the transcriptional and protein levels was significantly upregulated, even during infection. Simultaneously, myricetin also upregulated the anti-inflammatory cytokine IL-10 and suppressed the virus-induced pro-inflammatory factor TNF-α. In summary, this study indicates that myricetin may enhance the antiviral state by boosting the host's innate immune response. This highlights the potential of myricetin as a therapeutic candidate against PRRSV, providing a reference for the subsequent development of novel therapeutic agents.