AUTHOR=Liang Hui , Li Yu , Li Ming , Zhou Wei , Chen Jie , Zhang Zhen , Yang Yalin , Ran Chao , Zhou Zhigang 

TITLE=The effect and underlying mechanism of yeast β-glucan on antiviral resistance of zebrafish against spring viremia of carp virus infection

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1031962

DOI=10.3389/fimmu.2022.1031962

ISSN=1664-3224

ABSTRACT=<p>β-glucan has been used as immunostimulant for fish. However, the effect of yeast β-glucan on viral infections has been less studied in fish. In this study, we investigated the effects of β-glucan on the resistance of zebrafish against spring viraemia of carp virus (SVCV) and elucidated the underlying mechanisms. Zebrafish were fed with a control diet or diet supplemented with 0.01% and 0.025% β-glucan for 2 weeks, and were challenged by SVCV. Zebrafish embryonic fibroblast (ZF4) cells were treated with 5 μg/mL β-glucan and were infected by SVCV. We further investigated the effect of β-glucan on autophagy level post SVCV infection. The intestinal microbiota was evaluated by 16S <italic>r</italic>RNA gene pyrosequencing. Results showed that dietary supplementation of 0.025% β-glucan significantly increased survival rate of zebrafish compared with control group after SVCV challenge (<italic>P</italic> &lt; 0.05). Dietary β-glucan significantly increased the expression of genes related to type I IFN antiviral immune pathway in the spleen of zebrafish after viral infection, including type I IFN genes (<italic>ifnφ1</italic>, <italic>ifnφ2</italic>, <italic>ifnφ3</italic>), IFN-stimulated genes (<italic>mxb</italic>, <italic>mxc</italic>), as well as other genes involved in the IFN signaling pathway, including <italic>tlr7</italic>, <italic>rig1</italic>, <italic>mavs</italic>, <italic>irf3</italic> and <italic>irf7</italic>. Morpholino knockdown of type I IFN receptors dampened the antiviral effect of β-glucan in zebrafish larvae, indicating that β-glucan-mediated antiviral function was at least partially dependent on IFN immune response. Furthermore, β-glucan can inhibit the replication of SVCV in ZF4 cells. However, β-glucan did not stimulate type I IFN antiviral response in ZF4 cells, and the antiviral effect of β-glucan in ZF4 was independent of Myd88. Interestingly, β-glucan induced autophagy in ZF4 cells after SVCV infection. Inhibition of autophagy blocked the antiviral effect of β-glucan in ZF4 cells. Lastly, dietary β-glucan changed the composition of intestinal microbiota in zebrafish, with reduced abundance of Proteobacteria and an enrichment of Fusobacteria and Firmicutes. To sum up, our results indicate that the β-glucan enhanced resistance of zebrafish against SVCV and the mechanism involved stimulation of type I IFN antiviral immune response of fish after viral infection.</p>