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Published on: December 19, 2011
Phorbol Myristate Acetate Inhibits Senecavirus A Replication by Activating IKBKE-Mediated IFN Pathway and NF-κB
Junfang Yan1,2, Yanni Gao1, Chengyi Guo1
1Key Laboratory of Animal Diseases Diagnostic and Immunology, Ministry of Agriculture, MOE International Joint Collaborative Research Laboratory for Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China, njau.edu.cn.
Abstract:
Senecavirus A (SVA) is an emerging picornavirus causing vesicular disease indistinguishable from foot-and-mouth disease virus (FMDV). So far, there are no commercial vaccines and effective therapeutic drugs against SVA infection in China. Here, a library of 112 compounds were screened, and we found that phorbol myristate acetate plays an antagonistic role in the early stage of SVA infection. And phorbol 12-myristate 13-acetate (PMA) upregulates the expression of IKBKE, and activates IFN pathway and NF-κB signal. However, the PMA-mediated detrimental effect on SVA is reversed in IKBKE-deficient cells or when the NF-κB pathway blocked by BAY-117082, implying that IKBKE is the target for the antiviral effect of PMA. Additionally, PMA possesses antiviral effect on multiple RNA viruses, including porcine epidemic diarrhea virus (PEDV), porcine reproductive and respiratory syndrome virus (PRRSV), and encephalomyocarditis virus (EMCV). Overall, our findings offer that PMA inhibits SVA replication by activating IKBKE-mediated IFN pathway and NF-κB signal. And it might be a promising candidate for further broad-spectrum therapeutic development.
Insights
Phorbol 12-myristate 13-acetate (PMA) shows antiviral effects against Senecavirus A (SVA) by activating the IKBKE-mediated IFN and NF-κB pathways. This compound may offer a new therapeutic strategy for SVA and other RNA virus infections.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Senecavirus A (SVA) causes vesicular disease in swine, clinically indistinguishable from FMDV.
- Current treatments and vaccines for SVA are lacking in China.
- Emerging viral threats necessitate novel therapeutic strategies.
Purpose of the Study:
- To identify compounds with antiviral activity against SVA.
- To elucidate the mechanism of action for identified antiviral compounds.
- To explore the potential of identified compounds as broad-spectrum antiviral therapeutics.
Main Methods:
- Screening of 112 compounds for SVA inhibitory activity.
- Investigating the role of IKBKE and NF-κB signaling pathways.
- Testing antiviral activity against other RNA viruses (PEDV, PRRSV, EMCV).
Main Results:
- Phorbol 12-myristate 13-acetate (PMA) demonstrated antagonistic effects on early SVA infection.
- PMA upregulates IKBKE, activating IFN and NF-κB pathways.
- Antiviral effects were dependent on IKBKE expression and NF-κB pathway activity.
- PMA exhibited broad-spectrum activity against PEDV, PRRSV, and EMCV.
Conclusions:
- PMA inhibits SVA replication via the IKBKE-mediated IFN and NF-κB signaling pathways.
- IKBKE is identified as a key target for PMA's antiviral activity.
- PMA shows promise as a candidate for broad-spectrum antiviral therapeutic development.
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