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

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.

Maternal miR-202-5p is required for zebrafish primordial germ cell migration by protecting small GTPase Cdc42

In many lower animals,germ cell formation,migration,and maintenance depend on maternally provided determinants in germ plasm.In zebrafish,these processes have been extensively studied in terms of RNA-binding proteins and other coding genes.The role of small non-coding RNAs in the regulation of primordial germ cell(PGC)development remains largely unknown and poorly investigated,even though growing interests for the importance of miRNAs involved in a wide variety of biological processes.Here,we reported the role and mechanism of the germ plasm-specific miRNA miR-202-5p in PGC migration:(i)both maternal loss and knockdown of miR-202-5p impaired PGC migration indicated by the mislocalization and reduced number of PGCs;(ii)cdc42se1 was a direct target gene of miR-202-5p,and overexpression of Cdc42se1 in PGCs caused PGC migration defects similar to those observed in loss of miR-202-5p mutants;(iii)Cdc42se1 not only interacted with Cdc42 but also inhibited cdc42 transcription,and overexpression of Cdc42 could rescue PGC migration defects in Cdc42se1 overexpressed embryos.Thus,miR-202-5p regulates PGC migration by directly targeting and repressing Cdc42se1 to protect the expression of Cdc42,which interacts with actin to direct PGC migration.