Persistent hepatitis B virus infection in self-assembling microscale primary hepatocyte co-culture

An estimated 257 million patients are chronically infected with hepatitis B virus (HBV). Chronic HBV carriers are at risk of developing fibrosis, cirrhosis and hepatocellular carcinoma. A prophylactic vaccine exists and currently available antivirals can suppress viremia but rarely cure chronic infections. The study of HBV and the development of curative antivirals has been hampered by a scarcity of models that mimic infection in a physiologically relevant, cellular context. We have recently shown that cell-culture and patient-derived HBV can establish persistent infection for over 30 days in a self-assembling, primary hepatocyte co-culture (SACC-PHH) system. Building on our prior success in establishing HBV infection of SACC-PHHs in a 96 well plate format, we now report on efforts to characterize HBV infection in 384 well plates to make the system readily compatible with high-throughput screening for antiviral compounds.