Non-Targeted UHPLC-Q-TOF/MS-Based Metabolomics Reveals a Metabolic Shift from Glucose to Glutamine in CPB Cells during ISKNV Infection Cycle.

Xiaozhe Fu,Lihui Liu,Yinjie Niu,Shiwei Wu,Qiang Lin,Xixi Guo,Ningqiu Li,Hongru Liang

doi:10.3390/metabo9090174

Abstract

Infectious spleen and kidney necrosis virus (ISKNV) has caused serious economic losses in the cultured mandarin fish (Siniperca chuatsi) industry in China. Host metabolism alteration induced by disease infection may be the core problem of pathogenesis. However, to date, little is known about the disease-induced fish metabolism changes. In this study, we first reported ISKNV, the fish virus, induced metabolism alteration. The metabolomics profiles of Chinese perch brain cells (CPB) post-ISKNV infection at progressive time points were analyzed using the UHPLC-Q-TOF/MS technique. A total of 98 differential metabolites were identified. In the samples harvested at 24 hours post-infection (hpi; the early stage of ISKNV infection), 49 differential metabolites were identified comparing with control cells, including 31 up-regulated and 18 down-regulated metabolites. And in the samples harvested at 72 hpi (the late stage of ISKNV infection), 49 differential metabolites were identified comparing with control cells, including 27 up-regulated and 22 down-regulated metabolites. These differential metabolites were involved in many pathways related with viral pathogenesis. Further analysis on the major differential metabolites related to glucose metabolism and amino acid metabolism revealed that both glucose metabolism and glutamine metabolism were altered and a metabolic shift was determined from glucose to glutamine during ISKNV infection cycle. In ISKNV-infected cells, CPB cells prefer to utilize glucose for ISKNV replication at the early stage of infection, while they prefer to utilize glutamine to synthetize lipid for ISKNV maturation at the late stage of infection. These findings may improve the understanding of the interaction between ISKNV and host, as well as provide a new insight for elucidating the ISKNV pathogenic mechanism.

Highlights

Infectious kidney and spleen necrosis virus (ISKNV), an important viral pathogen of mandarin fish, is the type species of the genus Megalocytivirus, the family Iridoviridae [1]
In the samples harvested at 24 hours post-infection, 49 differential metabolites were identified comparing with control cells, including 31 up-regulated and 18 down-regulated metabolites
In the samples harvested at 72 hpi, 49 differential metabolites were identified comparing with control cells, including 27 up-regulated and 22 down-regulated metabolites

Summary

Introduction

Infectious kidney and spleen necrosis virus (ISKNV), an important viral pathogen of mandarin fish, is the type species of the genus Megalocytivirus, the family Iridoviridae [1]. ISKNV disease has caused great economic losses for the cultured mandarin fish ( known as Chinese perch) in China during the past few decades [2,3]. Because of its wide host range and high mortality for different fish species, ISKNV has been identified as one of the most important causative agents of fish and listed. The brain is not the target organ, ISKNV can be detected in the diseased fish brain. The transcriptome and proteome of CPB cells infected with ISKNV have been reported [8,9]. The ISKNV pathogenesis has not been fully understood to date

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