Hepatitis C Virus Dysregulates Polyamine and Proline Metabolism and Perturbs Urea Cycle

Natalia F. Zakirova; Olga A. Khomich; Olga A. Smirnova; Jennifer Molle; Sarah Duponchel; Dmitry V. Yanvarev; Vladimir T. Valuev-Elliston; Lea Monnier; Boyan Grigorov; Olga N. Ivanova; Inna L. Karpenko; Mikhail V. Golikov; Cedric Bovet; Barbara Rindlisbacher; Alex R. Khomutov; Sergey N. Kochetkov; Birke Bartosch; Alexander V. Ivanov

doi:10.20944/preprints202405.0025.v1

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preprints.org > biology and life sciences > virology > doi: 10.20944/preprints202405.0025.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Hepatitis C Virus Dysregulates Polyamine and Proline Metabolism and Perturbs Urea Cycle

Vladimir T. Valuev-Elliston

Barbara Rindlisbacher

Version 1 : Received: 29 April 2024 / Approved: 30 April 2024 / Online: 1 May 2024 (09:51:54 CEST)

How to cite: Zakirova, N. F.; Khomich, O. A.; Smirnova, O. A.; Molle, J.; Duponchel, S.; Yanvarev, D. V.; Valuev-Elliston, V. T.; Monnier, L.; Grigorov, B.; Ivanova, O. N.; Karpenko, I. L.; Golikov, M. V.; Bovet, C.; Rindlisbacher, B.; Khomutov, A. R.; Kochetkov, S. N.; Bartosch, B.; Ivanov, A. V. Hepatitis C Virus Dysregulates Polyamine and Proline Metabolism and Perturbs Urea Cycle. Preprints 2024, 2024050025. https://doi.org/10.20944/preprints202405.0025.v1 Zakirova, N. F.; Khomich, O. A.; Smirnova, O. A.; Molle, J.; Duponchel, S.; Yanvarev, D. V.; Valuev-Elliston, V. T.; Monnier, L.; Grigorov, B.; Ivanova, O. N.; Karpenko, I. L.; Golikov, M. V.; Bovet, C.; Rindlisbacher, B.; Khomutov, A. R.; Kochetkov, S. N.; Bartosch, B.; Ivanov, A. V. Hepatitis C Virus Dysregulates Polyamine and Proline Metabolism and Perturbs Urea Cycle. Preprints 2024, 2024050025. https://doi.org/10.20944/preprints202405.0025.v1

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MDPI and ACS Style

Zakirova, N. F.; Khomich, O. A.; Smirnova, O. A.; Molle, J.; Duponchel, S.; Yanvarev, D. V.; Valuev-Elliston, V. T.; Monnier, L.; Grigorov, B.; Ivanova, O. N.; Karpenko, I. L.; Golikov, M. V.; Bovet, C.; Rindlisbacher, B.; Khomutov, A. R.; Kochetkov, S. N.; Bartosch, B.; Ivanov, A. V. Hepatitis C Virus Dysregulates Polyamine and Proline Metabolism and Perturbs Urea Cycle. Preprints 2024, 2024050025. https://doi.org/10.20944/preprints202405.0025.v1

APA Style

Zakirova, N. F., Khomich, O. A., Smirnova, O. A., Molle, J., Duponchel, S., Yanvarev, D. V., Valuev-Elliston, V. T., Monnier, L., Grigorov, B., Ivanova, O. N., Karpenko, I. L., Golikov, M. V., Bovet, C., Rindlisbacher, B., Khomutov, A. R., Kochetkov, S. N., Bartosch, B., & Ivanov, A. V. (2024). Hepatitis C Virus Dysregulates Polyamine and Proline Metabolism and Perturbs Urea Cycle. Preprints. https://doi.org/10.20944/preprints202405.0025.v1

Chicago/Turabian Style

Zakirova, N. F., Birke Bartosch and Alexander V. Ivanov. 2024 "Hepatitis C Virus Dysregulates Polyamine and Proline Metabolism and Perturbs Urea Cycle" Preprints. https://doi.org/10.20944/preprints202405.0025.v1

Abstract

Hepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct acting antivirals were introduced into clinical practice. However, clearance of the virus does not reduce risk of end-stage liver diseases to the level observed in patients that have never been infected. So, investigation of HCV pathogenesis is still warranted. Virus-induced changes in cell metabolism contribute to the development of HCV-associated liver pathologies. Here we studied the impact of the virus on the metabolism of polyamines and proline as well as on the urea cycle, which plays a crucial role in liver function. It was found that HCV strongly suppresses the expression of arginase, a key enzyme of the urea cycle, leading to accumulation of arginine and upregulates proline oxidase with a concomitant decrease in proline concentrations. Addition of exogenous proline moderately suppressed viral replication. HCV upregulated transcription but suppressed protein levels of polyamine-metabolizing enzymes. This resulted in a decrease in polyamine content in infected cells. Finally, compounds targeting polyamine metabolism demonstrated pronounced antiviral activity pointing to spermine and spermidine as compounds affecting HCV replication. These data expand our understanding of HCV’s imprint on cell metabolism.

Keywords

hepatitis C virus; polyamines; urea cycle; proline metabolism; antiviral agents

Subject

Biology and Life Sciences, Virology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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