Research
Print page Print page
Switch language
Rigshospitalet - a part of Copenhagen University Hospital
Published

Antiviral Effect of Ribavirin against HCV Associated with Increased Frequency of G-to-A and C-to-U Transitions in Infectious Cell Culture Model

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Infants with congenital heart defects have reduced brain volumes

    Research output: Contribution to journalJournal articleResearchpeer-review

  2. Instrumental variable analysis using offspring BMI in childhood as an indicator of parental BMI in relation to mortality

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. De novo electrocardiographic abnormalities in persons living with HIV

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. Using machine learning for predicting intensive care unit resource use during the COVID-19 pandemic in Denmark

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Effect of liraglutide on expression of inflammatory genes in type 2 diabetes

    Research output: Contribution to journalJournal articleResearchpeer-review

  1. HIV infection is associated with type 2 diabetes mellitus

    Research output: Contribution to journalLetterResearchpeer-review

  2. De novo electrocardiographic abnormalities in persons living with HIV

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Central and peripheral nervous system complications of COVID-19: a prospective tertiary center cohort with 3-month follow-up

    Research output: Contribution to journalJournal articleResearchpeer-review

  4. HIV infection is associated with thoracic and abdominal aortic aneurysms: a prospective matched cohort study

    Research output: Contribution to journalJournal articleResearchpeer-review

  5. Enterovirus Meningitis in Adults: A Prospective Nationwide Population-Based Cohort Study

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Ribavirin (RBV) is a broad-spectrum antiviral active against a wide range of RNA viruses. Despite having been used for decades in the treatment of chronic hepatitis C virus (HCV) infection, the precise mechanism of action of RBV is unknown. In other viruses, it inhibits propagation by increasing the rate of G-to-A and C-to-U transitions. Here, we utilized the J6/JFH1 HCV cell-culture system to investigate whether RBV inhibits HCV through the same mechanism. Infected Huh7.5 cells were treated with increasing concentrations of RBV or its phosphorylated forms. A fragment of the HCV NS5B-polymerase gene was amplified, cloned, and sequenced to estimate genetic distances. We confirm that the antiviral effect of all three RBV-drug forms on HCV relies on induction of specific transitions (G-to-A and C-to-U). These mutations lead to generation of non-infectious virions, reflected by decreased spread of HCV in cell culture despite relatively limited effect on virus genome titers. Moreover, treatment experiments conducted on a novel Huh7.5 cell line stably overexpressing adenosine kinase, a key enzyme for RBV activation, yielded comparable results. This study indicates that RBV action on HCV in hepatoma cell-culture is exerted through increase in mutagenesis, mediated by RBV triphosphate, and leading to production of non-infectious viruses.

Original languageEnglish
JournalScientific Reports
Volume8
Issue number4619
ISSN2045-2322
DOIs
Publication statusPublished - 1 Mar 2018

    Research areas

  • Journal Article

ID: 53475336