Antibody-Mediated Porcine Reproductive and Respiratory Syndrome Virus Infection Downregulates the Production of Interferon-α and Tumor Necrosis Factor-α in Porcine Alveolar Macrophages via Fc Gamma Receptor I and III

Antibody-dependent enhancement (ADE) contributes to the pathogenesis of porcine reproductive and respiratory syndrome virus (PRRSV)-persistent infection. However, the mechanisms of PRRSV-ADE infection are still confusing. A clear understanding of the event upon virus infection by the ADE pathway has become crucial for developing efficient intervention of the PRRSV infection. In this study, an ADE assay showed that PRRSV-ADE infection in porcine alveolar macrophages (AMs) significantly decreased the production of interferon-alpha (IFN-alpha) and tumor necrosis factor-alpha (TNF-alpha), and significantly increased the production of interleukine-10 (IL-10). A gene knockdown assay based on small interfering RNA (siRNA) showed that both Fc gamma receptor I (Fc gamma RI) and Fc gamma RIII in porcine AMs were involved in PRRSV-ADE infection. An activation assay showed that specific activation of Fc gamma RI or Fc gamma RIII in porcine AMs during PRRSV infection not only significantly decreased the production of IFN-alpha and TNF-alpha, but also significantly increased the production of IL-10 and significantly facilitated PRRSV replication. In conclusion, our studies suggested that ADE downregulated the production of IFN-alpha and TNF-alpha in porcine AMs maybe via Fc gamma RI and Fc gamma RIII, thereby leading to enhanced PRRSV infection.