Abstract | BACKGROUND & AIMS: METHODS: Human primary hepatocytes and HuH7.5 cells were transiently transfected with the core protein of hepatitis C virus (HCV) genotypes 1a, 1b, and 2a. Infectious genotype 2a HCV in culture was also used. RESULTS: We show that HCV and core protein inhibit the phosphorylation of Serine 10 in histone 3. The inhibition is due to the direct interaction between HCV core and Aurora B kinase (AURKB) that results in a decrease of AURKB activity. HCV and core significantly downregulate NF-κB and COX-2 transcription, two proteins with anti-apoptotic and proliferative effects implicated in the control of the inflammatory response. AURKB depletion reduced HCV and core repression of NF-κB and COX-2 gene transcription and AURKB overexpression reversed the viral effect. AURKB abrogation increased HCV specific infectivity which was decreased when AURKB was overexpressed. CONCLUSIONS: The core-mediated decrease of AURKB activity may play a role in the inflammatory pathway during the initial steps of viral infection, while ensuring HCV infectivity.
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Authors | Antonio Madejón, Julie Sheldon, Irene Francisco-Recuero, Celia Perales, Mariela Domínguez-Beato, Marina Lasa, Isabel Sánchez-Perez, Jordi Muntané, Esteban Domingo, Javier García-Samaniego, Aurora Sánchez-Pacheco |
Journal | Journal of hepatology
(J Hepatol)
Vol. 63
Issue 2
Pg. 312-9
(Aug 2015)
ISSN: 1600-0641 [Electronic] Netherlands |
PMID | 25733156
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. |
Chemical References |
- RNA, Viral
- Aurora Kinase B
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Topics |
- Aurora Kinase B
(antagonists & inhibitors, metabolism)
- Biopsy
- Blotting, Western
- Genotype
- Hepacivirus
(genetics)
- Hepatitis C, Chronic
(genetics, metabolism, pathology)
- Hepatocytes
(metabolism, pathology)
- Humans
- RNA, Viral
(genetics)
- Real-Time Polymerase Chain Reaction
- Signal Transduction
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