Ipriflavone Inhibits Porcine Reproductive and Respiratory Syndrome Virus Infection via RIG-I/IRF3-Mediated Interferon Signaling

TL;DR

Ipriflavone, a natural compound, inhibits PRRSV infection in pigs by boosting immune signaling pathways that fight the virus.

Contribution

This study reveals that ipriflavone inhibits PRRSV replication by enhancing RIG-I/IRF3-mediated interferon signaling.

Findings

Ipriflavone inhibits PRRSV replication and assembly regardless of administration timing.

Ipriflavone activates RIG-I/IRF3 signaling to upregulate IFN-β and ISG56 expression.

Ipriflavone induces phosphorylation of IRF3 and STAT1, reducing viral replication.

Abstract

PRRSV remains one of the most significant pathogens that pose a serious threat to the pig farming industry. Ipriflavone is an isoflavone derivative available in various biological processes. In this study, we demonstrated that ipriflavone has anti-PRRSV activity and mainly disturbed PRRSV replication and assembly stages. In addition, ipriflavone could inhibit PRRSV replication via enhancing the RIG-I/IRF3-mediated I-IFN signaling pathway. These findings will provide insights into a potential therapy for PRRSV control.

Porcine reproductive and respiratory syndrome virus (PRRSV) remains one of the most important pathogens, resulting in huge economic losses to the global pig industry. Ipriflavone is an isoflavone derivative involved in various biological processes, showing anti-inflammatory, anti-apoptotic, antioxidant, and neuroprotective effects. However, the role of ipriflavone in antiviral immune response to PRRSV is unknown. In this study, we discovered that ipriflavone could significantly inhibit PRRSV replication. Moreover, ipriflavone inhibited PRRSV replication regardless of whether ipriflavone was added pre-, co-, or post-PRRSV infection, and ipriflavone mainly inhibited virus replication and assembly stages. Importantly, ipriflavone had the capacity to upregulate the expression levels of IFN-β and ISG56. Additionally, ipriflavone promoted the expression of RIG-I and MAVS, and induced phosphorylation of IRF3 and STAT1, while reducing PRRSV replication. Collectively, ipriflavone could enhance the RIG-I/IRF3 signaling pathway, thereby inhibiting PRRSV replication. These findings will provide an important theoretical basis for the development of therapeutic agents against PRRSV infection.

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