Work

Antibody-Dependent Enhancement of Porcine Reproductive and Respiratory Syndrome Virus Infection Antagonizes the Secretion of Type I Interferons in Porcine Alveolar Macrophages by Interfering with the Retinoic Acid-Inducible Gene I/Melanoma Differentiation-Associated Gene 5 Pathway via Fc Gamma Receptor I

Year: 2025

Type: article

Abstract: Type I interferons (IFNs), mainly IFN-α and IFN-β, play an essential role in defending against viral invasion by inducing the host's innate antiviral response. Porcine reproductive and respiratory syndrome virus (PRRSV) is known to impair the IFN responses of infected hosts through the antibody-dependent enhancement (ADE) infection pathway, but the precise mechanisms employed are poorly understood. In this study, we showed that PRRSV alone induced a strong secretion of IFN-α and IFN-β in infected porcine alveolar macrophages (PAMs) by activating the retinoic acid-inducible gene I (RIG-I)/melanoma differentiation-associated gene 5 (MDA5) signaling pathway. By contrast, ADE infection of PRRSV significantly down-regulated the production levels of IFN-α and IFN-β in PAMs by negatively regulating the RIG-I/MDA5 signaling pathway and considerably enhancing the replication level of PRRSV in PAMs. Next, small interfering RNA (siRNA) experiments revealed that Fc gamma receptor I (FcγRI) was responsible for the ADE infection of PRRSV in PAMs. In addition, we observed that FcγRI mediated the potent inhibition of IFN-α and IFN-β production through blocking the activation of the RIG-I/MDA5 signaling pathway in PAMs. Further, we found that FcγRI effectively inhibited PRRSV-induced synthesis of IFN-α and IFN-β by negatively regulating PRRSV-induced activation of the RIG-I/MDA5 signaling pathway in PAMs and significantly increased the viral production of PRRSV in PAMs. In conclusion, these results suggest that ADE infection of PRRSV may antagonize the secretion of type I IFNs (IFN-α/β) by interfering with the RIG-I/MDA5 pathway via FcγRI in PAMs, thereby facilitating the proliferation level of PRRSV in PAMs.

Source: Viruses

DOI: 10.3390/v17091277