α-Lipoic Acid Exerts Its Antiviral Effect against Viral Hemorrhagic Septicemia Virus (VHSV) by Promoting Upregulation of Antiviral Genes and Suppressing VHSV-Induced Oxidative Stress

  • Virol Sin. 2021 Dec;36(6):1520-1531. doi: 10.1007/s12250-021-00440-5.
Wanwan Zhang  1  2  3  4 ,  Xiaoqi Chen  1 ,  Fangzhao Yu  5 ,  Fengquan Li  1 ,  Wangdong Li  5 ,  Meisheng Yi  6  7  8  9 ,  Kuntong Jia  10  11  12  13
Affiliations
  • 1. School of Marine Sciences, Sun Yat-Sen University, Guangzhou, 510275, China.
  • 2. Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, 519000, China.
  • 3. Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Guangzhou, 510275, China.
  • 4. Pearl River Estuary Marine Ecosystem Research Station, Ministry of Education, Zhuhai, 519000, China.
  • 5. Modern Agricultural Development Center of Zhuhai City, Zhuhai, 519000, China.
  • 6. School of Marine Sciences, Sun Yat-Sen University, Guangzhou, 510275, China. [email protected].
  • 7. Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, 519000, China. [email protected].
  • 8. Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Guangzhou, 510275, China. [email protected].
  • 9. Pearl River Estuary Marine Ecosystem Research Station, Ministry of Education, Zhuhai, 519000, China. [email protected].
  • 10. School of Marine Sciences, Sun Yat-Sen University, Guangzhou, 510275, China. [email protected].
  • 11. Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Zhuhai, 519000, China. [email protected].
  • 12. Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering, Guangzhou, 510275, China. [email protected].
  • 13. Pearl River Estuary Marine Ecosystem Research Station, Ministry of Education, Zhuhai, 519000, China. [email protected].
PMID: 34510367 DOI: 10.1007/s12250-021-00440-5
Abstract

Viral hemorrhagic septicemia virus (VHSV), belonging to the genus Novirhabdovirus, Rhabdoviridae family, is a causative agent of high mortality in fish and has caused significant losses to the aquaculture industry. Currently, no effective vaccines, Food and Drug Administration-approved inhibitors, or Other therapeutic intervention options are available against VHSV. α-Lipoic Acid (LA), a potent antioxidant, has been proposed to have Antiviral effects against different viruses. In this study, LA (CC50 = 472.6 μmol/L) was repurposed to exhibit Antiviral activity against VHSV. In fathead minnow cells, LA significantly increased the cell viability post-VHSV Infection (EC50 = 42.7 μmol/L), and exerted a dose-dependent inhibitory effect on VHSV induced-plaque, cytopathic effects, and VHSV glycoprotein expression. The time-of-addition assay suggested that the Antiviral activity of LA occurred at viral replication stage. Survival assay revealed that LA could significantly upregulated the survival rate of VHSV-infected largemouth bass in both co-injection (38.095% vs. 1.887%, P < 0.01) and post-injection manner (38.813% vs. 8.696%, P < 0.01) compared with the control group. Additional comparative transcriptome and qRT-PCR analysis revealed LA treatment upregulated the expression of several Antiviral genes, such as IRF7, Viperin, and ISG15. Moreover, LA treatment reduced VHSV-induced Reactive Oxygen Species production in addition to Nrf2 and SOD1 expression. Taken together, these data demonstrated that LA suppressed VHSV replication by inducing Antiviral genes expression and reducing VHSV-induced oxidative stress. These results suggest a new direction in the development of potential Antiviral candidate drugs against VHSV Infection.

Keywords
Antiviral; IFN response; Oxidative stress; Viral hemorrhagic septicemia virus (VHSV); α-Lipoic acid (LA).
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