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In vitro hepatitis C virus infection and hepatic choline metabolism

Kaelan Gobeil Odai, Conor O’Dwyer, Rineke Steenbergen, Tyler A. Shaw, Tyler M. Renner, Peyman Ghorbani, Mojgan Rezaaifar, Shauna Han, Marc-André Langlois, Angela M. Crawley, Rodney S. Russell, John P. Pezacki, D. Lorne Tyrrell, View ORCID ProfileMorgan D. Fullerton
doi: https://doi.org/10.1101/746776
Kaelan Gobeil Odai
1Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada
2University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation
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Conor O’Dwyer
1Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada
2University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation
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Rineke Steenbergen
3Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada
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Tyler A. Shaw
4Department of Chemistry and Biomolecular Sciences, Faculty of Science, University of Ottawa, Ottawa, Canada
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Tyler M. Renner
1Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada
2University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation
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Peyman Ghorbani
1Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada
2University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation
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Mojgan Rezaaifar
1Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada
2University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation
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Shauna Han
1Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada
2University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation
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Marc-André Langlois
1Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada
2University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation
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Angela M. Crawley
1Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada
2University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation
5Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, Canada
6Department of Medicine, Division of Infectious Diseases, The Ottawa Hospital, Ottawa, Canada
7Department of Biology, Faculty of Science, Carleton University, Ottawa, Canada
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Rodney S. Russell
8Immunology and Infectious Diseases, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, Canada
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John P. Pezacki
1Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada
2University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation
4Department of Chemistry and Biomolecular Sciences, Faculty of Science, University of Ottawa, Ottawa, Canada
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D. Lorne Tyrrell
3Li Ka Shing Institute of Virology, Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada
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Morgan D. Fullerton
1Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, Canada
2University of Ottawa Centre for Infection, Immunity and Inflammation and Centre for Catalysis Research and Innovation
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  • ORCID record for Morgan D. Fullerton
  • For correspondence: morgan.fullerton@uottawa.ca
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Abstract

Choline is an essential nutrient required for normal neuronal and muscular development, as well as homeostatic regulation of hepatic metabolism. In the liver, choline is incorporated into the main eukaryotic phospholipid, phosphatidylcholine (PC) and can enter one carbon metabolism via mitochondrial oxidation. Hepatitis C virus (HCV) is a hepatotropic positive-strand RNA virus that similar to other positive-strand RNA viruses can impact phospholipid metabolism. In the current study we sought to interrogate the link between choline transport and early HCV infection. Namely, we aimed to investigate how HCV modulates markers of choline metabolism following in vitro infection, while subsequently assessing how the inhibition of choline uptake and metabolism upon concurrent HCV infection may alter early viral replication. Finally, we assessed whether these parameters were consistent between cells cultured in fetal bovine serum (FBS) or human serum (HS), conditions known to differentially affect in vitro HCV infection. We observed that choline transport in FBS-cultured Huh7.5 cells is facilitated by the intermediate affinity transporter choline transporter-like family (CTL), and that CTL1 expression and the incorporation of choline into PC is diminished in 24 h infected FBS-cultured cells. Reciprocally, limiting the availability of choline for PC synthesis resulted in increased HCV replication at this early stage. In chronically HS-cultured Huh7.5 cells, there were no differences in the expression of choline transporters upon HCV infection or alterations to viral replication when choline transport was inhibited compared to control treatments. However, inhibiting choline uptake and metabolism in this system significantly impaired the production of infectious virions in HS-cultured cells. These results suggest that in addition to a known role of choline kinase, the transport of choline, potentially via CTL1, might also represent an important and regulated process during HCV infection.

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Posted August 25, 2019.
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In vitro hepatitis C virus infection and hepatic choline metabolism
Kaelan Gobeil Odai, Conor O’Dwyer, Rineke Steenbergen, Tyler A. Shaw, Tyler M. Renner, Peyman Ghorbani, Mojgan Rezaaifar, Shauna Han, Marc-André Langlois, Angela M. Crawley, Rodney S. Russell, John P. Pezacki, D. Lorne Tyrrell, Morgan D. Fullerton
bioRxiv 746776; doi: https://doi.org/10.1101/746776
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In vitro hepatitis C virus infection and hepatic choline metabolism
Kaelan Gobeil Odai, Conor O’Dwyer, Rineke Steenbergen, Tyler A. Shaw, Tyler M. Renner, Peyman Ghorbani, Mojgan Rezaaifar, Shauna Han, Marc-André Langlois, Angela M. Crawley, Rodney S. Russell, John P. Pezacki, D. Lorne Tyrrell, Morgan D. Fullerton
bioRxiv 746776; doi: https://doi.org/10.1101/746776

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