Decremental effect of non-host humoral milieu interfacing viral envelope on the RNA level and surface antigenicity of hepatitis C virus (HCV) in vitro

Backgrounds: Hepatitis C virus (HCV) has infected an estimated 170 million people worldwide, most of whom are chronic patient of HCV. However, the lack of standard in vitro culture system and suitable animal model for this virus hampers fundamental conquest against HCV infection. Methods: We evaluated whether humoral milieu such as serum or culture media, and its constituents, lipid and electrolyte and pH might affect the RNA level and envelope status of HCV in vitro, fnally increasing the infection effciency of HCV in vitro and in vivo. Results: We found that the RNA level of HCV is favorable in human serum, albeit adverse in mouse serum and Dulbecco’s Modifed Eagle Medium (DMEM), and the surface antigenicity in mouse serum showed higher than human serum and DMEM. Consistently, viral clearance was verifed by the increase of anti-HCV core ELISA assay in mouse serum and DMEM. Lipid analysis revealed that the LDL-cholesterol was decreased in the presence of HCV. In lipid removal analysis, the level of genome in mouse serum was signifcantly lower than human serum. For electrolytes analysis, the level of potassium in human serum was signifcantly lower than mouse serum and DMEM. Last, the RNA level and surface antigenicity of HCV in DMEM was significantly augmented in a pH-dependent manner, and the acidity showed higher the RNA level and surface antigenicity than neutral pH. Conclusion: This study clearly shows that the non-host humoral milieu such as mouse, and DMEM decreases the RNA level and surface antigenicity, clinically implying the decremental infectivity of HCV virions. This is the frst note to tune HCV viability via conditioning only host humoral milieu free of genetic approach.