Global Metabolic Profiling of Baculovirus Infection in Silkworm Hemolymph Shows the Importance of Amino-Acid Metabolism.

Min Feng,Hongyun Wu,Mengmeng Zhang,Luc Swevers,Shigang Fei,Junming Xia,Jingchen Sun

doi:10.3390/v13050841

Abstract

Viruses rely on host cell metabolism to provide the necessary energy and biosynthetic precursors for successful viral replication. Infection of the silkworm, Bombyx mori, by Bombyx mori nucleopolyhedrovirus (BmNPV), has been studied extensively in the past to unravel interactions between baculoviruses and their lepidopteran hosts. To understand the interaction between the host metabolic responses and BmNPV infection, we analyzed global metabolic changes associated with BmNPV infection in silkworm hemolymph. Our metabolic profiling data suggests that amino acid metabolism is strikingly altered during a time course of BmNPV infection. Amino acid consumption is increased during BmNPV infection at 24 h post infection (hpi), but their abundance recovered at 72 hpi. Central carbon metabolism, on the other hand, particularly glycolysis and glutaminolysis, did not show obvious changes during BmNPV infection. Pharmacologically inhibiting the glycolytic pathway and glutaminolysis also failed to reduce BmNPV replication, revealing that glycolysis and glutaminolysis are not essential during BmNPV infection. This study reveals a unique amino acid utilization process that is implemented during BmNPV infection. Our metabolomic analysis of BmNPV-infected silkworm provides insights as to how baculoviruses induce alterations in host metabolism during systemic infection.

Highlights

Viruses are considered the ultimate parasites, and the materials needed for their life activities must be provided by their host
Bombyx mori nucleopolyhedrovirus (BmNPV) infection in hemocytes (Supplementary Data Sheet S4). These results suggest that glutamine catabolism, glycolysis, and tricarboxylic acid (TCA) cycle were not activated by BmNPV infection
Viruses need to target host cell metabolism to ensure their efficient replication, and the host will take several measures at various levels to counterbalance the use of its metabolites by the virus

Summary

Introduction

Viruses are considered the ultimate parasites, and the materials needed for their life activities must be provided by their host. Viruses typically depend on the host cell to obtain the building blocks and biosynthesis machinery needed for virion replication and assembly [1,2,3]. A large amount of new knowledge has been obtained on the interaction between virus and host through mRNA transcriptome and proteome analysis, but these approaches do not directly describe the use of cellular metabolites by viruses. There is no doubt that viral infection triggers metabolic reprogramming in host cells to facilitate virus production [1,2,3]. High-throughput technologies for the analysis of metabolic alterations in host cells (“metabolomics”) have recently become widely available and have greatly expanded our knowledge of these crucial host-viruses interactions [3,4]. Newcastle disease virus infection increased pools of amino acids and nucleotides to benefit viral protein synthesis and genome amplification [6]

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Conclusion