Metabolic reprogramming of the host cells during lymphocytic choriomeningitis virus infection

Authors: Lucia Baďurová 1    Božena Omasta 2    Ingrid Ovečková 3    Katarína Polčicová 3    Jana Tomášková 3   
1 Department of Genetics, Faculty of Natural Sciences, Comenius University in Bratislava, Slovakia    2 Department of Microbiology and Virology, Faculty of Natural Sciences, Comenius University in Bratislava, Slovakia    3 Department of Virus Ecology, Institute of Virology, Biomedical Research Center of the Slovak Academy of Sciences, Slovakia   
Year: 2020
Section: Cellular metabolism, physiology, molecular biology and genetics
Abstract No.: 1907
ISBN: 978-80-972360-6-9

Viruses, as obligate intracellular parasites, are solely dependent on the metabolic machinery of their host cells. To ensure an optimal environment for their replication, many viruses have developed different strategies how to modulate the cellular metabolic pathways. Moreover, the alterations of cellular metabolism during virus infection often resemble metabolic reprogramming in cancer cells. Both conditions often stimulate the uptake of extracellular nutrients and predominantly modulate glucose, glutamine and fatty acid metabolism.

The interaction between the metabolism of the host cells and arenavirus infection remains unclear. Our study shed light on these processes during lymphocytic choriomeningitis virus (LCMV) infection that is a model representative of the Arenaviridae family. The main objectives of the present study were as follows: (i) the gene expression analysis of transporters and enzymes involved in glucose and glutamine metabolism during distinct stages of acute LCMV infection; (ii) monitoring the effect of glucose or glutamine deficiency on the infectious virion production; (iii) determining the essentiality of LCMV-induced metabolic changes by pharmacological inhibition of particular enzymes involved in glucose or glutamine utilization.

In LCMV-infected cells, we identified various alterations of glucose and glutamine metabolism at the gene expression level. Predominant changes were observed 24- and 72-hours post-infection that correspond to the viremic and post-viremic stage of LCMV infection, respectively. LCMV-infection led to increased expression of many genes, which products are involved in the glucose or glutamine uptake and in the process of glycolysis or glutaminolysis. However, depriving LCMV-infected cells of extracellular glucose or glutamine and pharmacological inhibition of the glutaminolytic pathway had no impact on the infectious virion production. Unexpectedly, we observed a significant antiviral effect of the commonly used glycolytic inhibitor 2-deoxy-D-glucose (2-DG) on LCMV propagation. Our further experiments have shown that the negative impact of 2-DG on the life cycle of LCMV is not caused by the inhibition of glycolysis but by the impairment of the viral glycoprotein precursor (GP-C) N-glycosylation. Unglycosylated GP‑C was not effectively cleaved to functional products, thus reducing LCMV infectious virion production.

Our study has highlighted several metabolic changes during LCMV infection, which will require further analysis to elucidate the precise mechanism in relation to the LCMV life cycle. Moreover, we identified a significant negative impact of 2-DG on LCMV propagation that is associated with impaired glycosylation of the viral GP-C. Since 2-DG inhibits replication of many viruses by acting on various cellular targets, it may serve as a potential candidate for a broad-spectrum antiviral therapy.

This project was supported by grant 2/0030/19 from the Scientific Grant Agency of the Ministry of Education, Science, Research and Sport of the Slovak Republic and Slovak Academy of Sciences.