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

K A S N Shanaka; Sumi Jung; K P Madushani; Myoung-Jin Kim; Jehee Lee

doi:10.3389/fimmu.2023.1327749

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

Front Immunol. 2023 Dec 19:14:1327749. doi: 10.3389/fimmu.2023.1327749. eCollection 2023.

Authors

K A S N Shanaka^#^{1

2}, Sumi Jung^#^{1

2}, K P Madushani^#¹, Myoung-Jin Kim³, Jehee Lee^{1

2}

Affiliations

¹ Department of Marine Life Sciences & Fish Vaccine Research Center, Jeju National University, Jeju, Republic of Korea.
² Marine Science Institute, Jeju National University, Jeju, Republic of Korea.
³ Bioresource Industrialization Center, Nakdonggang National Institute of Biological Resources, Sangju-si, Gyeongsangbuk-do, Republic of Korea.

^# Contributed equally.

Abstract

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, viperin ^-/- fish showed considerably higher mortality rates. VHSV copy number and the expression of the NP gene were significantly increased in viperin ^-/- fish. Metabolic gene analysis revealed significant differences in soda, hif1a, fasn, and acc expression, indicating their impact on metabolism. Cholesterol analysis in zebrafish larvae during VHSV infection showed significant upregulation of cholesterol production without Viperin. In vitro 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 viperin. Neutrophil and macrophage recruitment were significantly modulated in viperin ^-/- 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.

Keywords: RNA virus; VHSV; Viperin; antiviral protein; zebrafish.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cholesterol
Hemorrhagic Septicemia, Viral*
Mammals
Perciformes*
Proteins
Viperin Protein / metabolism
Zebrafish
Zebrafish Proteins / metabolism

Substances

Cholesterol
Proteins
Viperin Protein
Zebrafish Proteins

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF), funded by the Ministry of Education (2019R1A6A1A03033553) and supported by the Korea Institute of Marine Science & Technology Promotion (KIMST), funded by the Ministry of Oceans and Fisheries (20220570).