AUTHOR=Shanaka K. A. S. N. , Jung Sumi , Madushani K. P. , Kim Myoung-Jin , Lee Jehee 

TITLE=Viperin mutation is linked to immunity, immune cell dynamics, and metabolic alteration during VHSV infection in zebrafish

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1327749

DOI=10.3389/fimmu.2023.1327749

ISSN=1664-3224

ABSTRACT=<p>Viperin is a prominent antiviral protein found in animals. The primary function of Viperin is the production of 3’-deoxy-3’,4’-didehydro-cytidine triphosphate (ddhCTP), an inhibitory nucleotide involved in viral RNA synthesis. Studies in mammalian models have suggested that ddhCTP interferes with metabolic proteins. However, this hypothesis has yet to be tested in teleost. In this study, the role of Viperin in regulating metabolic alterations during viral hemorrhagic septicemia virus (VHSV) infection was tested. When infected with VHSV, <italic>viperin</italic><sup>-/-</sup> fish showed considerably higher mortality rates. VHSV copy number and the expression of the <italic>NP</italic> gene were significantly increased in <italic>viperin</italic><sup>-/-</sup> fish. Metabolic gene analysis revealed significant differences in <italic>soda</italic>, <italic>hif1a</italic>, <italic>fasn</italic>, and <italic>acc</italic> expression, indicating their impact on metabolism. Cholesterol analysis in zebrafish larvae during VHSV infection showed significant upregulation of cholesterol production without Viperin. <italic>In vitro</italic> analysis of ZF4 cells suggested a considerable reduction in lipid production and a significant upregulation of reactive oxygen species (ROS) generation with the overexpression of <italic>viperin</italic>. Neutrophil and macrophage recruitment were significantly modulated in <italic>viperin</italic><sup>-/-</sup> fish compared to the wild-type (WT) fish. Thus, we have demonstrated that Viperin plays a role in interfering with metabolic alterations during VHSV infection.</p>