The composition of the hepatitis B surface antigen (HBsAg) in acute hepatitis B virus (HBV) infections is reproducible in an in vitro model

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Background and aims The surface antigen of hepatitis B virus (HBV), HBsAg, consists of the components large (L), middle (M) and small (S)HBs. The composition of HBsAg differs across disease stages, is an early marker for treatment induced HBsAg loss and possibly a marker for HBV integration. However, the role of HBsAg components in the HBV life cycle is largely unknown. We aimed at establishing an in vitro model of HBV infections based on primary human hepatocytes (PHHs) and patient-derived HBV to investigate the composition of the HBsAg proteins during the natural course of in vitro HBV infections. Methods PHHs were infected with HBV from serum of a chronically infected patient. Supernatant of the infected cells was collected daily. LHBs, MHBs and total HBsAg as well as HBV DNA and HBV RNA were quantified using validated in-house-systems. In addition, the HBsAg components were measured in sera of acutely infected (n=3) and chronically infected patients. Results De novo HBV infection started 4 days post infection (dpi). Total levels of HBsAg increased from 37 ng at day 3 to 94 ng at day 4 and 213 ng/mL at day 7. De novo secretion of HBV DNA and RNA began 5-6 dpi and after 8 dpi, infection remained stable over 14 days. During the in vitro infection, the MHBs ratios were higher (7.9-16.9%) compared to LHBs (2.7-4.6%). The composition of HBsAg in acutely infected patients revealed similar proportions at week 4 after diagnosis of the HBV infection. Thus, mean percentages of MHBs and LHBs were 9.4 (3.5-24-6) % and 3.6 (0.8-5.0)% in those patients, respectively. In contrast, HBsAg composition was different in patients with chronic HBV infections. Conclusion We could establish an in vitro model of HBV infection with high levels and similar composition of HBsAg as acute in vivo infections. Our model may help to reveal the mechanisms of HBsAg clearance and HBV integration. Publication History Article published online: 08 September 2020 © Georg Thieme Verlag KG Stuttgart · New York

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