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  

作　　者：Wanwan Zhang Xiaoqi Chen Fangzhao Yu Fengquan Li Wangdong Li Meisheng Yi Kuntong Jia 

机构地区：[1]School of Marine Sciences,Sun Yat-Sen University,Guangzhou 510275,China [2]Modern Agricultural Development Center of Zhuhai City,Zhuhai 519000,China [3]Southern Marine Science and Engineering Guangdong Laboratory(Zhuhai),Zhuhai 519000,China [4]Guangdong Provincial Key Laboratory of Marine Resources and Coastal Engineering,Guangzhou 510275,China [5]Pearl River Estuary Marine Ecosystem Research Station,Ministry of Education,Zhuhai 519000,China

出　　处：《Virologica Sinica》2021年第6期1520-1531,共12页中国病毒学（英文版）

基　　金：This work was supported by the Pearl River S&T Nova Program of Guangzhou(201806010047);the National Natural Science Foundation of China(31771587);Fundamental Research Funds for the Central Universities。

摘　　要：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(CC_(50)= 472.6 lmol/L) was repurposed to exhibit antiviral activity against VHSV. In fathead minnow cells,LA significantly increased the cell viability post-VHSV infection(EC_(50)= 42.7 lmol/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 q RT-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.

关 键 词：Viral hemorrhagic septicemia virus(VHSV) α-Lipoic acid(LA) ANTIVIRAL IFN response Oxidative stress 

分 类 号：S941.413[农业科学—水产养殖]