Detection of the hepatitis B virus (HBV) covalently-closed-circular DNA (cccDNA) in mice transduced with a recombinant AAV-HBV vector.
Fiche publication
Date publication
septembre 2017
Journal
Antiviral research
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAUMERT Thomas
Tous les auteurs :
Lucifora J, Salvetti A, Marniquet X, Mailly L, Testoni B, Fusil F, Inchauspé A, Michelet M, Michel ML, Levrero M, Cortez P, Baumert TF, Cosset FL, Challier C, Zoulim F, Durantel D
Lien Pubmed
Résumé
Hepatitis B Virus (HBV) persists in infected hepatocytes as an episomal covalently-closed-circular DNA mini-chromosome, called cccDNA. As the main nuclear transcription template, HBV cccDNA is a key replication intermediate in the viral life cycle. Little is known about the mechanisms involved in its formation, maintenance and fate under antiviral therapies. This is mainly due to the lack of small immune-competent animal models able to recapitulate the entire HBV replication cycle, including formation of HBV cccDNA. Here we report that HBV cccDNA can be detected by Southern blot analyses in the liver of C57BL6 mice transduced with AAV-HBV. HBV cccDNA persists in the liver of these animals together with the AAV-HBV episome. We also set up a PCR strategy to distinguish the HBV cccDNA from the AAV-HBV episome. These suggest that the AAV-HBV/mouse model might be relevant to test drugs targeting HBV cccDNA regulation and persistence.
Mots clés
Animals, Blotting, Southern, DNA Replication, DNA, Circular, isolation & purification, DNA, Viral, isolation & purification, Dependovirus, genetics, Disease Models, Animal, Genetic Vectors, Hepatitis B, drug therapy, Hepatitis B virus, genetics, Hepatocytes, virology, Liver, virology, Mice, Plasmids, Polymerase Chain Reaction, methods, Transduction, Genetic
Référence
Antiviral Res.. 2017 Sep;145:14-19