Hepatitis B virus sensitivity to interferon‐α in hepatocytes is more associated with cellular interferon response than with viral genotype

• DOI: 10.1002/hep.29609
• Publication Date: 2017-10-23T19:05:26Z
• Authors: Fang Shen; Yaming Li; Yang Wang; Vitina Sozzi; Peter A. Revill; Jiangxia Liu; Lu Gao; Guang Yang; Mengji Lu; Kathrin Sutter; Ulf Dittmer; Jieliang Chen; Zhenghong Yuan
• Keywords: 0301 basic medicine; Hepatitis B virus; Genotype; Blotting, Western; Medizin; Cell Culture Techniques; 610; Interferon-alpha; Hepatitis B; Real-Time Polymerase Chain Reaction; Virus Replication; Antiviral Agents; 3. Good health; 03 medical and health sciences; DNA, Viral; Hepatocytes; Humans

Interferon-α (IFN-α) is used to treat chronic hepatitis B virus (HBV) infection, but only 20%-40% of patients respond well. Clinical observations have suggested that HBV genotype associated with the response IFN therapy; however, its role in viral responsiveness HBV-infected hepatocytes remains unclear. Here, we produced infectious virions genotypes A D infect three well-recognized cell-culture-based infection systems, including primary human (PHH), differentiated HepaRG (dHepaRG), and HepG2-NTCP cells quantitatively compare antiviral effect IFN-α on across cell models. The efficacy against was generally similar A2, B5, C2, D3; it significantly different among models given half maximal inhibitory concentration value for inhibition DNA replication PHH (<20 U/mL) dHepaRG were much lower than (>500 U/mL). Notably, even PHH, did not reduce covalently closed circular at concentrations which antigens intermediates strongly reduced. cell-culture exhibited differential cellular IFN-α. genes reported be robustly induced while weakly upon treatment. Reduction or promotion attenuated improved capacity replication, respectively.In models, sensitivity determined more by cell-intrinsic genotype, improvement promotes HBV. (Hepatology 2018;67:1237-1252).