Regulatory effect of humoral milieu on the viral DNA and surface antigen expression of hepatitis B virus (HBV) in vitro

Backgrounds: While a few virions of hepatitis B virus (HBV) are sufficient to liver infection in vivo, even a large quantity of virion is unable to enter into hepatoma cells in vitro. Methods: To solve this paradox, we explored if humoral milieu such as serum or culture media, and its constituents, and pH would regulate the viral DNA and surface antigen expression of HBV in vitro. Results: The viral DNA and surface antigen expression of HBV are significantly more stable in human serum than in mouse serum, and Dulbecco's Modified eagle Medium (DMEM). In line, the increase of anti-HBcAg antibody in mouse serum, and DMEM implies that the virion was cleared in non-host humoral milieu. Further, lipid analysis revealed higher levels of lipids in human serum than those in mouse serum, and DMEM. Lipid removal analysis showed the decreased level of HBV DNA and surface antigen expression in human and mouse serum. In electrolytes analysis, human serum contained lower level of potassium than mouse serum. Last, on the viral DNA and surface antigen expression of HBV, the alkalinity of DMEM was more effective than neutral pH. Conclusion: Collectively, this study indicates that humoral milieu would regulate the viral DNA and surface antigen expression of HBV in vitro. This is the first report to regulate HBV growth/viability via simple manipulation of host humoral milieu.