1. Academic Validation
  2. 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

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

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].
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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