Abstract
BackgroundPorcine circovirus type 2 (PCV2) is an important and common DNA virus that infect pig and can cause immunosuppression and induce apoptosis in the infected cells. To escape the host immune system, PCV2 constantly builds up complex mechanisms or mutates genes, and that is why it is difficult to eradicate complex PCV2 infection by relying on vaccines and single compound. At present, there is few literature reports on the effective prevention and treatment of PCV2 infection by a combination of two or more compounds. Previously, we have demonstrated the anti-PCV2 effect of Matrine in vitro, but its mechanism has not been further evaluated. Literatures have proven that Osthole has a variety of pharmacological activities, and we tested the ability of Osthole to inhibit PCV2 replication in cell culture. Therefore, this study explored the synergistic antiviral effect of Matrine combined with Osthole and their synergistic anti-apoptotic mechanism.ResultsOsthole alone had an anti-PCV2 effect, and then its synergistic anti-PCV2 effect of Osthole and Matrine was better than that of Matrine or Osthole alone as demonstrated by qRT-PCR, IFA and Western blotting results. The anti-apoptotic mechanism of these two compounds by inducing the PERK pathway by PCV2 was elucidated through Annexin V-FITC/PI, JC-1 and Western blotting. Matrine and Osthole combination could inhibit the expression of Cap in Cap-transfected PK-15 cells, thus inhibiting Cap-induced PERK apoptosis. Ribavirin was used as a positive control.ConclusionsThe combination of Osthole and Matrine had the synergistic effect of anti-PCV2 infection by directly inhibiting the expression of PCV2 Cap protein. The combination of these two compounds also inhibited PERK apoptosis induced by PCV2 Cap protein, possibly by regulating the level of GRP78. The results formed a base for further studies on the mechanism of anti-PCV2 in vivo using Matrine and Osthole combination and developing new anti-PCV2 compounds with Cap and GRP78 as therapeutic targets.
Highlights
Porcine circovirus type 2 (PCV2) is an important and common DNA virus that infect pig and can cause immunosuppression and induce apoptosis in the infected cells
PCV2 is the smallest single-stranded cyclic DNA virus with an unencapsulated membrane in animal, and the capsid protein (Cap) encoded by the ORF2-encoded gene of PCV2 is considered as a major viral structural protein and a primary immunogen involved in the replication of PCV2 [2]
This study has provided the theoretical basis for the further studies on the mechanism of anti-PCV2 in vivo using Matrine combined with Osthole and developing new antiviral compounds
Summary
Porcine circovirus type 2 (PCV2) is an important and common DNA virus that infect pig and can cause immunosuppression and induce apoptosis in the infected cells. To escape the host immune system, PCV2 constantly builds up complex mechanisms or mutates genes, and that is why it is difficult to eradicate complex PCV2 infection by relying on vaccines and single compound. It is necessary to study the synergistic anti-PCV2 effect of two or more compound combinations through multiple targets or pathways. Keeping this in view, based on the guidance of traditional Chinese veterinary medicine theory, when two or more compounds with various pharmacological activities are combined reasonably, a component prescription with clear chemical composition and mechanism of action is formed, which is conducive to exerting synergistic pharmacological effects through multi-targets and multi-pathway, and will provide a new concept for the future research and development of Chinese veterinary drugs
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