Correlation of Virus and Host Response Markers with Circulating Immune Complexes during Acute and Chronic Woodchuck Hepatitis Virus Infection

Abstract

ABSTRACT Woodchuck hepatitis virus (WHV) is an established model for human hepatitis B virus. The kinetics of virus and host responses in serum and liver during acute, self-limited WHV infection in adult woodchucks were studied. Serum WHV DNA and surface antigen (WHsAg) were detected as early as 1 to 3 weeks following experimental infection and peaked between 1 and 5 weeks postinfection. Thereafter, serum WHsAg levels declined rapidly and became undetectable, while WHV DNA levels became undetectable much later, between 4 and 20 weeks postinfection. Decreasing viremia correlated with transient liver injury marked by an increase in serum sorbitol dehydrogenase (SDH) levels. Clearance of WHV DNA from serum was associated with the normalization of serum SDH. Circulating immune complexes (CICs) of WHsAg and antibodies against WHsAg (anti-WHs) that correlated temporarily with the peaks in serum viremia and WHs antigenemia were detected. CICs were no longer detected in serum once free anti-WHs became detectable. The detection of CICs around the peak in serum viremia and WHs antigenemia in resolving woodchucks suggests a critical role for the humoral immune response against WHsAg in the early elimination of viral and subviral particles from the peripheral blood. Individual kinetic variation during WHV infections in resolving woodchucks infected with the same WHV inoculum and dose is likely due to the outbred nature of the animals, indicating that the onset and magnitude of the individual immune response determine the intensity of virus inhibition and the timing of virus elimination from serum.