biostudies-literatureZakirova NF111 ProjectThe DevWeCan French Laboratories of Excellence NetworkRussian Science FoundationANRS-MIEDevWeCan French Laboratories of Excellence Network1036https://www.ebi.ac.uk/biostudies/studies/S-EPMC11201506biostudies-literatureUnknown13(12)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 the risk of end-stage liver diseases to the level observed in patients who 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 thCellsHepatitis C Virus Dysregulates Polyamine and Proline Metabolism and Perturbs the Urea Cycle.PMC11201506B12003ANR-10-LABX-612215719-74-10086Molle JValuev-Elliston VTSmirnova OAIvanov AVZakirova NFBovet CGrigorov BIvanova ONRindlisbacher BBartosch BKarpenko ILKhomutov ARMonnier LYanvarev DVDuponchel SKhomich OAKochetkov SNGolikov MVfalseHepatitis C Virus Dysregulates Polyamine and Proline Metabolism and Perturbs the Urea Cycle.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 the risk of end-stage liver diseases to the level observed in patients who 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 th2024-01-01T00:00:00Z2024 Jun2026-04-08T19:06:29.629Z2025-02-19T00:16:04.508ZS-EPMC112015063892066410.3390/cells13121036