College of Veterinary Medicine, Henan Agricultural University, Zhengdong New District Longzi Lake 15#, Zhengzhou 450046, China.
College of Life Science, Henan Agricultural University, Zhengdong New District Longzi Lake 15#, Zhengzhou 450046, China.
Viruses. 2023 Mar 17;15(3):777. doi: 10.3390/v15030777.
Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus 2 (PCV2) are economically important pathogens in swine, and pigs with dual infections of PCV2 and PRRSV consistently have more severe clinical symptoms and interstitial pneumonia. However, the synergistic pathogenesis mechanism induced by PRRSV and PCV2 co-infection has not yet been illuminated. Therefore, the aim of this study was to characterize the kinetic changes of immune regulatory molecules, inflammatory factors and immune checkpoint molecules in porcine alveolar macrophages (PAMs) in individuals infected or co-infected with PRRSV and/or PCV2. The experiment was divided into six groups: a negative control group (mock, no infected virus), a group infected with PCV2 alone (PCV2), a group infected with PRRSV alone (PRRSV), a PCV2-PRRSV co-infected group (PCV2-PRRSV inoculated with PCV2, followed by PRRSV 12 h later), a PRRSV-PCV2 co-infected group (PRRSV-PCV2 inoculated with PRRSV, followed by PCV2 12 h later) and a PCV2 + PRRSV co-infected group (PCV2 + PRRSV, inoculated with PCV2 and PRRSV at the same time). Then, PAM samples from the different infection groups and the mock group were collected at 6, 12, 24, 36 and 48 h post-infection (hpi) to detect the viral loads of PCV2 and PRRSV and the relative quantification of immune regulatory molecules, inflammatory factors and immune checkpoint molecules. The results indicated that PCV2 and PRRSV co-infection, regardless of the order of infection, had no effect on promoting PCV2 replication, while PRRSV and PCV2 co-infection was able to promote PRRSV replication. The immune regulatory molecules (IFN-α and IFN-γ) were significantly down-regulated, while inflammatory factors (TNF-α, IL-1β, IL-10 and TGF-β) and immune checkpoint molecules (PD-1, LAG-3, CTLA-4 and TIM-3) were significantly up-regulated in the PRRSV and PCV2 co-infection groups, especially in PAMs with PCV2 inoculation first followed by PRRSV. The dynamic changes in the aforementioned immune molecules were associated with a high viral load, immunosuppression and cell exhaustion, which may explain, at least partially, the underlying mechanism of the enhanced pulmonary lesions by dual infection with PCV2 and PRRSV in PAMs.
猪繁殖与呼吸综合征病毒（PRRSV）和猪圆环病毒 2 型（PCV2）是猪的两种重要经济病原，同时感染 PCV2 和 PRRSV 的猪通常具有更严重的临床症状和间质性肺炎。然而，PRRSV 和 PCV2 共感染诱导的协同发病机制尚未阐明。因此，本研究旨在描述单独感染 PRRSV 和/或 PCV2 以及共感染 PRRSV 和 PCV2 的猪肺泡巨噬细胞（PAMs）中免疫调节分子、炎症因子和免疫检查点分子的动态变化。该实验分为六组：阴性对照组（无感染病毒）、单独感染 PCV2 组（PCV2）、单独感染 PRRSV 组（PRRSV）、PCV2-PRRSV 共感染组（先接种 PCV2，12 小时后接种 PRRSV）、PRRSV-PCV2 共感染组（先接种 PRRSV，12 小时后接种 PCV2）和 PCV2+PRRSV 共感染组（同时接种 PCV2 和 PRRSV）。然后，在感染后 6、12、24、36 和 48 小时收集不同感染组和对照组的 PAM 样本，检测 PCV2 和 PRRSV 的病毒载量以及免疫调节分子、炎症因子和免疫检查点分子的相对定量。结果表明，无论感染顺序如何，PCV2 和 PRRSV 共感染均不会促进 PCV2 复制，而 PRRSV 和 PCV2 共感染能够促进 PRRSV 复制。PRRSV 和 PCV2 共感染组的免疫调节分子（IFN-α 和 IFN-γ）显著下调，而炎症因子（TNF-α、IL-1β、IL-10 和 TGF-β）和免疫检查点分子（PD-1、LAG-3、CTLA-4 和 TIM-3）显著上调，特别是先接种 PCV2 后接种 PRRSV 的 PAMs 中。上述免疫分子的动态变化与高病毒载量、免疫抑制和细胞衰竭有关，这至少部分解释了 PCV2 和 PRRSV 双重感染在 PAMs 中增强肺部病变的潜在机制。
