公开(公告)号：US20200377892A1

公开(公告)日：2020-12-03

申请号：US16643293

申请日：2018-08-31

申请人： INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM) ,  HOSPICES CIVILS DE LYON ,  Centre Léon-Bérard ,  Centre national de la recherche scientifique ,  Université Claude Bernard Lyon 1

发明人： Jean Pierre QUIVY ,  Barbara TESTONI ,  Fabien ZOULIM ,  Maelle LOCATELLI

IPC分类号： C12N15/113

摘要： The present invention concerns an inhibitor for use for preventing and/or treating an infection with hepatitis B virus (HBV) and an in vitro screening method for the identification of a candidate compound suitable for preventing and/or treating an infection with hepatitis B virus. Inventors show that the knock-down of histone chaperone HIRA before HBV inoculation led to a strong decrease in HBV cccDNA (covalently closed circular DNA) accumulation and stable rcDNA (relaxed circular DNA) levels, in HepG2-NTCP cell line, indicating either a possible incomplete or delayed rcDNA to cccDNA transition. This effect was independent from HBx protein expression in Primary human hepatocytes (PHH). HIRA is able to interact with cccDNA and its recruitment is concomitant with deposition of histone variant H3.3 in HepG2-NTCP cell line. HIRA was able to interact with HBc (HBV capsid protein) in infected hepatocytes and in an HepaRG cell line expressing HBc in an inducible manner.