College of Animal Science and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, China.
Viruses. 2020 Feb 8;12(2):187. doi: 10.3390/v12020187.
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-α (IFN-α) and tumor necrosis factor-α (TNF-α), 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 (FcγRI) and FcγRIII in porcine AMs were involved in PRRSV-ADE infection. An activation assay showed that specific activation of FcγRI or FcγRIII in porcine AMs during PRRSV infection not only significantly decreased the production of IFN-α and TNF-α, 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-α and TNF-α in porcine AMs maybe via FcγRI and FcγRIII, thereby leading to enhanced PRRSV infection.
抗体依赖性增强（ADE）作用导致猪繁殖与呼吸综合征病毒（PRRSV）持续性感染的发生。然而，PRRSV-ADE 感染的机制仍不清楚。明确 ADE 途径感染病毒时的情况，对于开发 PRRSV 感染的有效干预措施至关重要。在本研究中，ADE 检测显示 PRRSV-ADE 感染猪肺泡巨噬细胞（AMs）会显著降低干扰素-α（IFN-α）和肿瘤坏死因子-α（TNF-α）的产生，而显著增加白细胞介素-10（IL-10）的产生。基于小干扰 RNA（siRNA）的基因敲低检测显示，Fcγ 受体 I（FcγRI）和 FcγRIII 都参与了 PRRSV-ADE 感染。激活检测显示，在 PRRSV 感染期间，猪 AMs 中 FcγRI 或 FcγRIII 的特异性激活不仅显著降低了 IFN-α 和 TNF-α的产生，还显著增加了 IL-10 的产生，并显著促进了 PRRSV 的复制。综上所述，我们的研究表明，ADE 通过 FcγRI 和 FcγRIII 下调了猪 AMs 中 IFN-α和 TNF-α的产生，从而导致 PRRSV 感染增强。
