The Scorpion Venom Peptide Smp76 Inhibits Viral Infection by Regulating Type-I Interferon Response
Dengue virus (DENV) and Zika virus (ZIKV) have spread throughout many countries in the developing world and infect millions of people every year, causing severe harm to human health and the economy. Unfortunately, there are few effective vaccines and therapies available against these viruses. Therefore, the discovery of new antiviral agents is critical. Herein, a scorpion venom peptide (Smp76) characterized from Scorpio maurus palmatus was successfully expressed and purified in Escherichia coli BL21(DE3). The recombinant Smp76 (rSmp76) was found to effectively inhibit DENV and ZIKV infections in a dose-dependent manner in both cultured cell lines and primary mouse macrophages. Interestingly, rSmp76 did not inactivate the viral particles directly but suppressed the established viral infection, similar to the effect of interferon (IFN)-β. Mechanistically, rSmp76 was revealed to upregulate the expression of IFN-β by activating interferon regulatory transcription factor 3 (IRF3) phosphorylation, enhancing the type-I IFN response and inhibiting viral infection. This mechanism is significantly different from traditional virucidal antimicrobial peptides (AMPs). Overall, the scorpion venom peptide Smp76 is a potential new antiviral agent with a unique mechanism involving type-I IFN responses, demonstrating that natural AMPs can enhance immunity by functioning as immunomodulators.
KeywordsDengue virus (DENV) Zika virus (ZIKV) Scorpion venom peptide Smp76 Antiviral mechanism Type-I interferon response
We are indebted to Dr. Bo Zhang from the Wuhan Institute of Virology, Chinese Academy of Sciences for kindly providing DENV serotype-2 TSV01 strain. We thank Dr. Ren Sun and Dr. Danyang Gong from the University of California, Los Angeles for sharing pBR322-Z2 plasmid. We gratefully acknowledge Prof. Wu Jianguo and Prof. Bo Zhong from Wuhan University for their kindly providing DENV-2 (NGC) and Ifnar1-/- mice, respectively. This work was supported by grants from National Science Fund of China (Nos. 31572289, 31872239 and 81630091), International S&T Cooperation Program of China (No. S2016G3110), Hubei Science Fund (Nos. 2015CFA042 and 2016CFA018), China-Kazakhstan Cooperation Program (No. CK-07-09), and Fundamental Research Funds for the Central Universities in China (Nos. 2042017kf0242 and 2042017kf0199). SAA is grateful for financial support from Higher Education Commission (HEC) of Pakistan.
FFL, ZQX, XCG and ZLJ designed the experiments and analyzed the data. ZLJ, FS and MJG performed most of the experiments. ZLJ and YTC wrote the manuscript. SAA, WXL, YLW and ZJC revised the manuscript. All authors read and approved the final manuscript.
Compliance with Ethics Standards
Conflict of interest
The authors declare that they have no competing interests.
Animal and Human Rights Statement
All animal experiments were in accordance with and were approved by the Institutional Animal Care and Use Committee of Wuhan University (Wuhan, China).
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