Temporal pathogenesis of experimental neonatal woodchuck hepatitis virus infection: Increased initial viral load and decreased severity of acute hepatitis during the development of chronic viral infection

Acute hepatitis B virus (HBV) infections either resolve or progress to chro nicity. Identification of early deviations in host-virus responses associat ed with these outcomes can further differentiate cause-effect mechanisms th at Initiate and maintain chronicity. Neonatal woodchucks were infected expe rimentally with the woodchuck hepatitis virus (WHV) at 3 days of age. At 8 or 14 weeks of age (i.e., the early- or mid-acute stage of infection), whol e blood and large surgical biopsies of the liver were obtained from infecte d animals and uninfected controls. These were stored for later correlating histopathologic responses and viral load with the subsequently determined o utcome of infection. As of 1 year postinfection, half of the surgically tre ated infected woodchucks had developed self-limited infections, while the o ther half developed chronic infections. The self-limited outcome was charac terized by decreased viral load in acute-phase liver and plasma and a gener ally robust acute hepatic inflammatory response. Comparisons at the same ea rly time points revealed that the chronic outcome was characterized by incr easing initial viral load in liver and plasma, and a detectable, but dimini shed, acute hepatic inflammation. These cotemporal comparisons indicate tha t there is an early host-response deviation during the acute phase of a dev eloping chronic infection. Continued analysis of the tissues banked from th is study will facilitate further temporal characterization of acute-phase m echanisms that determine resolution versus chronicity in WHV infection. Und erstanding such mechanisms may be useful in the rational design of therapy for established chronic HBV infection.