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

doi:10.3390/v12010108

Viruses (Jan 2020)

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

Affiliations

Kaelan Gobeil Odai: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Conor O’Dwyer: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Rineke Steenbergen: Department of Medical Microbiology and Immunology and Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB T6G 2E1, Canada
Tyler A. Shaw: Department of Chemistry and Biomolecular Sciences, Faculty of Science, University of Ottawa, Ottawa, ON K1N 6N5, Canada
Tyler M. Renner: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Peyman Ghorbani: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Mojgan Rezaaifar: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Shauna Han: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Marc-André Langlois: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Angela M. Crawley: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
Rodney S. Russell: Immunology and Infectious Diseases, Faculty of Medicine, Memorial University of Newfoundland, St. John’s, NL A1B 3V6, Canada
John P. Pezacki: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada
D. Lorne Tyrrell: Department of Medical Microbiology and Immunology and Li Ka Shing Institute of Virology, University of Alberta, Edmonton, AB T6G 2E1, Canada
Morgan D. Fullerton: Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada

DOI: https://doi.org/10.3390/v12010108
Journal volume & issue: Vol. 12, no. 1
p. 108

Abstract

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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 and can impact phospholipid metabolism. In the current study we sought to interrogate if HCV modulates markers of choline metabolism following in vitro infection, while subsequently assessing if the inhibition of choline uptake and metabolism upon concurrent HCV infection alters viral replication and infectivity. Additionally, 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- and HS-cultured Huh7.5 cells is facilitated by the intermediate affinity transporter, choline transporter-like family (CTL). HCV infection in FBS, but not HS-cultured cells diminished CTL1 transcript and protein expression at 24 h post-infection, which was associated with lower choline uptake and lower incorporation of choline into PC. No changes in other transporters were observed and at 96 h post-infection, all differences were normalized. Reciprocally, limiting the availability of choline for PC synthesis by use of a choline uptake inhibitor resulted in increased HCV replication at this early stage (24 h post-infection) in both FBS- and HS-cultured cells. Finally, in chronic infection (96 h post-infection), inhibiting choline uptake and metabolism significantly impaired the production of infectious virions. 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.

Published in Viruses

ISSN: 1999-4915 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.mdpi.com/journal/viruses

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