Occult persistence and lymphotropism of hepadnaviral infection: insights from the woodchuck viral hepatitis model.

Hepatitis B virus (HBV) is a major human pathogen that causes chronic infection and life-threatening liver diseases in millions of individuals. While pathological and epidemiological consequences of clinically evident HBV infections are well recognized, there is no similar knowledge on an asymptomatic, silently progressing virus persistence. Contrary to previous opinion, current evidence indicates that a serologically undetectable (occult) HBV carriage is a common outcome of recovery from symptomatic illness and that scanty amounts of the virus are carried by apparently healthy individuals for years after resolution of hepatitis B despite the presence of presumably protective antiviral antibodies. Recent studies on this silent form of hepadnavirus carriage in an experimental woodchuck hepatitis virus (WHV) infection, which is considered to be the closest natural model of HBV disease, revealed that the life-long occult persistence of traces of pathogenic virus is an invariable consequence of recovery after hepadnaviral invasion and that this state always co-exists with a steady low-rate virus replication in both the liver and the lymphatic system. Importantly, this serologically concealed infection can be accompanied by development of hepatocellular carcinoma in convalescent animals and is transmittable from mothers to offspring as an asymptomatic, indefinitely long infection which involves the lymphatic system but not always the liver. This review focuses on the features of hepadnavirus occult persistence and its lymphotropism, and on what is currently understood about the contribution of the lymphatic system in maintaining hepadnavirus carriage based on insights provided by analysis of the woodchuck-WHV experimental system.