Establishment of a human hepatocellular cell line capable of maintaining long-term replication of hepatitis B virus.
Hepatitis B virus (HBV) is a virus whose replication cycle cannot be completely reproduced using cultured cell lines. Here, we report an engineered cell line capable of supporting the complete HBV life cycle. We generated HepG2 cells over-expressing the HBV entry receptor human NTCP (sodium taurocholate cotransporting polypeptide), and defective in RIG-I (retinoic acid-inducible gene-I)-like receptor signaling, by knocking down the IPS-1 (IFNβ-promoter stimulator-1) adaptor molecule. The resultant NtG20.i7 cells were susceptible to HBV, and its replication was detectable at 14 days post-infection and persisted for at least 35 days with a gradual increase of HBV core expression. The cells produced infectious HBV in the culture supernatant, and the addition of preS1 peptide myr47-WT, which blocks HBV entry, impaired the persistence of the infection. These findings suggest that the persistence of the infection was maintained by continuous release of infectious HBV virions and their re-infection. This system is useful for expanding our basic understanding of the HBV replication cycle and for screening of anti-HBV chemicals.
['Yao|Wan-Ling|WL|', 'Ikeda|Sotaro|S|', 'Tsukamoto|Yuta|Y|', 'Shindo|Keiko|K|', 'Otakaki|Yukie|Y|', 'Qin|Mian|M|', 'Iwasawa|Yoshikazu|Y|', 'Takeuchi|Fumihiko|F|', 'Kaname|Yuki|Y|', 'Chou|Yu-Chi|YC|', 'Chang|Chungming|C|', 'Watashi|Koichi|K|', 'Wakita|Takaji|T|', 'Noda|Takeshi|T|', 'Kato|Hiroki|H|', 'Fujita|Takashi|T|']
D048868:Adaptor Proteins, Signal Transducing D000071457:DEAD Box Protein 58 D056945:Hep G2 Cells D006515:Hepatitis B virus D022781:Hepatocytes D006801:Humans D029363:Organic Anion Transporters, Sodium-Dependent D011971:Receptors, Immunologic D015398:Signal Transduction D027981:Symporters D014779:Virus Replication
NTCP IPS-1 HBV infection/replication RIG-I-like receptor signaling innate immunity