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 infec tion and life-threatening liver diseases in millions of individuals. While pathological and epidemiological consequences of clinically evident HBV inf ections are well recognized, there is no similar knowledge on an asymptomat ic, silently progressing virus persistence Contrary to previous opinion, cu rrent evidence indicates that a serologically undetectable (occult) HBV car riage is a common outcome of recovery from symptomatic illness and that sca nty amounts of the virus are carried by apparently healthy individuals for years after resolution of hepatitis B despite the presence of presumably pr otective antiviral antibodies. Recent studies on this silent form of hepadn avirus carriage in an experimental woodchuck hepatitis virus (WHV) infectio n, which is considered to be the closest natural model of HBV disease, reve aled that the life-long occult persistence or 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 bo th the liver and the lymphatic system. Importantly, this serologically conc ealed infection can be accompanied by development of hepatocellular carcino ma in convalescent animals and is transmittable from mothers to offspring a s an asymptomatic, indefinitely long infection which involves the lymphatic system but not always the liver This review focuses on the features of hep adnavirus occult persistence and its lymphotropism, and on what is currentl y understood about the contribution of the lymphatic system in maintaining hepadnavirus carriage based on insights provided by analysis of the woodchu ck-WHV experimental system.