Exploration of the Role of Cyclophilins in Established Hepatitis B and C Infections
Cyclophilin (Cyp) inhibitors are of clinical interest in respect to their antiviral activities in the context of many viral infections including chronic hepatitis B and C. Cyps are a group of enzymes with peptidyl-prolyl isomerase activity (PPIase), known to be required for replication of diverse vi...
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2024-12-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/17/1/11 |
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| author | Jennifer Molle Sarah Duponchel Jennifer Rieusset Michel Ovize Alexander V. Ivanov Fabien Zoulim Birke Bartosch |
| author_facet | Jennifer Molle Sarah Duponchel Jennifer Rieusset Michel Ovize Alexander V. Ivanov Fabien Zoulim Birke Bartosch |
| author_sort | Jennifer Molle |
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| description | Cyclophilin (Cyp) inhibitors are of clinical interest in respect to their antiviral activities in the context of many viral infections including chronic hepatitis B and C. Cyps are a group of enzymes with peptidyl-prolyl isomerase activity (PPIase), known to be required for replication of diverse viruses including hepatitis B and C viruses (HBV and HCV). Amongst the Cyp family, the molecular mechanisms underlying the antiviral effects of CypA have been investigated in detail, but potential roles of other Cyps are less well studied in the context of viral hepatitis. Furthermore, most studies investigating the role of Cyps in viral hepatitis did not investigate the potential therapeutic effects of their inhibition in already-established infections but have rather been performed in the context of neo-infections. Here, we investigated the effects of genetically silencing Cyps on persistent HCV and HBV infections. We confirm antiviral effects of CypA and CypD knock down and demonstrate novel roles for CypG and CypH in HCV replication. We show, furthermore, that CypA silencing has a modest but reproducible impact on persistent HBV infections in cultured human hepatocytes. |
| format | Article |
| id | doaj-art-ef7ca861bdd04d93b4993b1b14dd287b |
| institution | Kabale University |
| issn | 1999-4915 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj-art-ef7ca861bdd04d93b4993b1b14dd287b2025-01-24T13:52:14ZengMDPI AGViruses1999-49152024-12-011711110.3390/v17010011Exploration of the Role of Cyclophilins in Established Hepatitis B and C InfectionsJennifer Molle0Sarah Duponchel1Jennifer Rieusset2Michel Ovize3Alexander V. Ivanov4Fabien Zoulim5Birke Bartosch6INSERM U1052, CNRS UMR5286, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, Lyon Hepatology Institute (IHU Everest), 69003 Lyon, FranceINSERM U1052, CNRS UMR5286, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, Lyon Hepatology Institute (IHU Everest), 69003 Lyon, FranceCarMeN Laboratory, INSERM U1060, INRA U1397, Lyon Hepatology Institute, 69007 Lyon, FranceCarMeN Laboratory, INSERM U1060, INRA U1397, Lyon Hepatology Institute, 69007 Lyon, FranceCenter for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991 Moscow, RussiaINSERM U1052, CNRS UMR5286, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, Lyon Hepatology Institute (IHU Everest), 69003 Lyon, FranceINSERM U1052, CNRS UMR5286, Université Claude Bernard Lyon 1, Hospices Civils de Lyon, Lyon Hepatology Institute (IHU Everest), 69003 Lyon, FranceCyclophilin (Cyp) inhibitors are of clinical interest in respect to their antiviral activities in the context of many viral infections including chronic hepatitis B and C. Cyps are a group of enzymes with peptidyl-prolyl isomerase activity (PPIase), known to be required for replication of diverse viruses including hepatitis B and C viruses (HBV and HCV). Amongst the Cyp family, the molecular mechanisms underlying the antiviral effects of CypA have been investigated in detail, but potential roles of other Cyps are less well studied in the context of viral hepatitis. Furthermore, most studies investigating the role of Cyps in viral hepatitis did not investigate the potential therapeutic effects of their inhibition in already-established infections but have rather been performed in the context of neo-infections. Here, we investigated the effects of genetically silencing Cyps on persistent HCV and HBV infections. We confirm antiviral effects of CypA and CypD knock down and demonstrate novel roles for CypG and CypH in HCV replication. We show, furthermore, that CypA silencing has a modest but reproducible impact on persistent HBV infections in cultured human hepatocytes.https://www.mdpi.com/1999-4915/17/1/11hepatitis viruscyclophilinliveranti-viral treatment |
| spellingShingle | Jennifer Molle Sarah Duponchel Jennifer Rieusset Michel Ovize Alexander V. Ivanov Fabien Zoulim Birke Bartosch Exploration of the Role of Cyclophilins in Established Hepatitis B and C Infections Viruses hepatitis virus cyclophilin liver anti-viral treatment |
| title | Exploration of the Role of Cyclophilins in Established Hepatitis B and C Infections |
| title_full | Exploration of the Role of Cyclophilins in Established Hepatitis B and C Infections |
| title_fullStr | Exploration of the Role of Cyclophilins in Established Hepatitis B and C Infections |
| title_full_unstemmed | Exploration of the Role of Cyclophilins in Established Hepatitis B and C Infections |
| title_short | Exploration of the Role of Cyclophilins in Established Hepatitis B and C Infections |
| title_sort | exploration of the role of cyclophilins in established hepatitis b and c infections |
| topic | hepatitis virus cyclophilin liver anti-viral treatment |
| url | https://www.mdpi.com/1999-4915/17/1/11 |
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