Department of Preventive Veterinary Medicine, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, People's Republic of China.
Department of Preventive Veterinary Medicine, Key Laboratory of Animal Epidemiology of the Ministry of Agriculture, College of Veterinary Medicine, China Agricultural University, 2 Yuanmingyuan West Road, Haidian District, Beijing 100193, People's Republic of China.
Virus Res. 2022 Oct 2;319:198854. doi: 10.1016/j.virusres.2022.198854. Epub 2022 Jul 1.
It is a common phenomenon that PRRSV infection can interfere with the protective efficacy of the CSFV vaccine in clinical settings, and no effective treatment is available. In our previous study, we found that PRRSV infection could inhibit the replication of CSFV-C by promoting the high expression of inflammatory cytokines. In order to further investigate whether Chinese medicine could alleviate the inhibition effect, the PAM39 cells model, which was co-infected with PRRSV and CSFV-C, was established. The effects of Chinese medicine on this co-infection model, as well as the effect of astragalus polysaccharide on the TLRs/NF-κB/TNF-α pathways, were investigated. Our results demonstrated that PAM39 cells inoculated with different pathogenic PRRSV significantly inhibited the replication of CSFV-C and up-regulated the major inflammatory mediators, including TNF-α. For the following studies, 50 µM of astragalus polysaccharide was selected from six kinds of representative Chinese medicine based on their cytotoxicity, viral titers, and inflammatory mediators. Further experiments indicated that astragalus polysaccharide could alleviate the inhibition of CSFV-C replication in the co-infection group with no influence on cell viability. In addition, astragalus polysaccharide treatment clearly reduced P65 phosphorylation and down-regulated the expression of TLR7, TLR9, and TNF-α in co-infection group, implying that the TLRs/NF-κB/TNF-α pathways may play an important role in astragalus polysaccharide's anti-inflammatory response. In conclusion, astragalus polysaccharide treatment alleviated PRRSV-mediated inhibition of CSFV-C replication via the TLRs/NF-κB/TNF-α pathways, and the molecular mechanism of PRRSV co-infection leading to the failure of CSFV vaccine immunization was partially elucidated, providing a scientific basis for effective CSF prevention and control in pig farms.
猪繁殖与呼吸综合征病毒（PRRSV）感染会干扰猪瘟病毒（CSFV）疫苗在临床环境中的保护效果，且目前尚无有效的治疗方法，这是一种常见现象。在我们之前的研究中发现，PRRSV 感染可通过促进炎症细胞因子的高表达来抑制 CSFV-C 的复制。为了进一步研究中药是否能缓解这种抑制作用，我们建立了 PRRSV 和 CSFV-C 共感染的 PAM39 细胞模型，研究了中药对这种共感染模型的影响，以及黄芪多糖对 TLRs/NF-κB/TNF-α 通路的影响。我们的结果表明，用不同致病性 PRRSV 接种的 PAM39 细胞显著抑制了 CSFV-C 的复制，并上调了主要的炎症介质，包括 TNF-α。在接下来的研究中，根据细胞毒性、病毒滴度和炎症介质，我们从六种代表性中药中选择了 50 μM 的黄芪多糖。进一步的实验表明，黄芪多糖可以缓解共感染组中 CSFV-C 复制的抑制作用，而对细胞活力没有影响。此外，黄芪多糖处理明显降低了共感染组中 P65 的磷酸化水平，并下调了 TLR7、TLR9 和 TNF-α 的表达，表明 TLRs/NF-κB/TNF-α 通路可能在黄芪多糖的抗炎反应中发挥重要作用。综上所述，黄芪多糖通过 TLRs/NF-κB/TNF-α 通路缓解了 PRRSV 介导的 CSFV-C 复制抑制，部分阐明了 PRRSV 共感染导致 CSFV 疫苗免疫失败的分子机制，为猪场有效防控猪瘟提供了科学依据。
