Virion half-life in chronic hepatitis B virus infection is strongly correlated with viral load

Abstract

Little is known about the mechanisms determining clearance rates of hepatitis B virus (HBV) in chronically infected individuals. Mathematical modeling of viral kinetics may reveal new aspects of this disease. During chronic infection, the rates of viral production and clearance are in balance and determine virion half-life. Methods: Using the relationship between intracellular relaxed circular DNA (rcDNA) and extracellular virions in blood, we performed viral dynamic analysis by quantifying viral loads in serum and in the liver of both treatment naïve chronically HBV-infected patients (N=80), and immunodeficient uPA mice (N=7) repopulated with tupaia hepatocytes and infected with woolly monkey (WM) HBV. Results: We show that free virion clearance in chronic HBV infection can be very rapid and is strongly correlated with viral load (p<0.0001, r=0,83): median half-life was 46 minutes for HBeAg-positive individuals harboring median 4,5×107 HBV-DNA copies/ml serum and a remarkably short 150 seconds for HBeAg-negative individuals with significantly lower median serum HBV-DNA levels (6,5×104 HBV-DNA/ml). Virion half-life in high viremic (4,6×108 WMHBV-DNA copies/ml) immunodeficient uPA mice was similar (90 min) to estimates determined in patients with comparable high titers, suggesting that the fast clearance rates of free virions in high viremic chronic carriers are determined by common non-immune specific mechanisms. However, virion half-life in mice was less dependent on viral load, suggesting that immune components can significantly reduce free virion half-life in chronically HBV-infected individuals with low viral loads.