Astragalus polysaccharide alleviated the inhibition of CSFV C-strain replication caused by PRRSV via the TLRs/NF‑κB/TNF-α pathways

Abstract

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.

Keywords: Anti-inflammatory; Astragalus polysaccharide; CSFV; Co-infection; Immune failure; PRRSV.