NMR-based metabolomics revealed metabolic changes in energy production for viral replication and immunological response in rock bream (Oplegnathus fasciatus) tissues during rock bream iridovirus (RBIV) infection

Abstract

Outbreaks of rock bream iridovirus (RBIV) infection in rock bream (Oplegnathus fasciatus) were continuously recorded, and these infections lead to vast economic losses in the aquaculture industry. However, metabolomic, proteomic, and transcriptomic studies in rock bream infected with RBIV are limited. In this study, metabolic responses in tissues of rock bream with different infection degrees of control (0C) and heavy-infected fish (0H) at 0 week, and fish with low viral titer at 3 week (3 L)-were observed by high-resolution magic-angle spinning (HR-MAS) NMR spectroscopy-based metabolomics, with multivariate, and pathway-based analyses being used to aid interpretation. In the liver, significant metabolic pathways related to energy metabolism such as glutamine and glutamate metabolism and the TCA cycle were observed only in 0H. Additionally, 0C and 3 L were clustered in the OPLS-DA (orthogonal partial least squares discriminant analysis) score plot, and 3 L showed no significant pathways compared to 0C. Thus, it is assumed that lightly infected fish (3 L) were survived from heavy-infection after 3 weeks. In the spleen, the metabolites relevant to energy production and immune response including pyruvate metabolism, the TCA cycle and branched-chain amino acid (BCAA) metabolism were changed in 0H. These results suggest that RBIV induced rapid and high energy production in the spleen by promoting both the Warburg effect, and the TCA cycle for their replication. In the kidney, elevation of the kynurenine pathway, which is related to the immunological response, and decreased osmolytes such as trimethylamine N-oxide and betaine were observed in 0H. We found that RBIV induced various disturbances in metabolism in host cells through viral replication and protective responses in the host. This study is the first metabolomics study of rock bream infected in RBIV using HR-MAS NMR spectroscopy, providing insights into how cellular metabolism is affected during RBIV infection. These results can be used as a resource to evaluate the mechanism of host-pathogen interactions.