Hepadnaviruses, their infections and hepatocellular carcinoma

Ten years ago hepatitis B virus (HBV) was thought to be a unique virus, not included in any known family of viruses. Following the discovery of a number of HBV-like viruses that infect birds and mammals, the existence of a new family known as hepadnaviridae has been confirmed. Hepadnaviruses are small hepatotropic viruses that have a characteristic partially double stranded genome, exhibit a narrow host range and replicate by reverse transcription. The family currently comprises six viruses of which human hepatitis B virus is the prototype member. Other members include woodchuck hepatitis virus (WHV), ground squirrel hepatitis virus (GSHV), tree squirrel hepatitis virus (TSHV). Peking duck hepatitis B virus (DHBV) and heron hepatitis B virus (HHBV). Candidate members of the family include kangaroo hepatitis virus (KHV) and stink snake hepatitis virus (SSHV). In humans, infection with HBV is associated with a wide spectrum of clinical conditions including acute and chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC). Infection with HBV is endemic throughout much of the world and the virus is maintained by the enormous reservoir of over 300 million chronic carriers. For almost 20 years experimental work on hepadnaviruses has been carried out using either natural hosts or cultured cells that were capable to support synthesis of a few viral gene products but unable to execute a complete cycle of virus replication. In this article, we have attempted to summarize the efforts made towards understanding the biology of hepadnaviruses, the nature of their infections and their association with primary liver cancer.