ABSTRACT

Viral hepatitis means liver inflammation caused by a viral infection. MacCallum was the first to introduce the terms hepatitis A and hepatitis B, in 1947, to sort out infectious (epidemic) from serum hepatitis (Fields et al., 2001; Thomas et al., 2005). In 1965, Blumberg found an antigen in patients with serum type hepatitis (type B hepatitis) and was initially named “Australian Antigen” (now known as hepatitis B surface antigen) (Fields et al., 2001; Thomas et al., 2005). The virion was first seen in the electron microscope by Dane in 1970, who clearly described its structure and correctly interpreted the nature of the associated smaller particles and tubular forms (Monjardino, 1998). It was hence known as the Dane particle. Soon after, the core of the virion was identified in infected hepatocytes and also isolated from complete virions following detergent removal of the envelope. Major advances during the early seventies, to which Robinson’s group at Stanford was a main contributor, led to the characterization of the virus genome, virion-associated proteins (including DNA polymerase) and the major HBV antigens and antiHBV antibodies present during HBV infections. As techniques for cloning and amplification of DNA became available, the virus genome was sequenced and putative genes identified. In 1982, the elegant experiments of Summers and Mason characterized the mechanism of replication and opened up a new phase in HBV research (Monjardino, 1998; Fields et al., 2001; Thomas et al., 2005).

Human HBV and animal hepatitis viruses share common characteristics, which are the basis for their classification as hepadnaviruses (HBV being the prototype of the Hepadnaviridae family). The Woodchuck hepatitis virus (WHV, 1978), the Ground squirrel hepatitis virus (GSHV, 1980), and the Tree squirrel hepatitis virus (TSHV, 1986) are mammalian hepadnaviruses (Orthohepadnavirus genus), while the Duck hepatitis B virus (DHBV, 1980) and the Heron hepatitis B virus (HHBV, 1988) are avian hepadnaviruses (Avihepadnavirus genus) (Monjardino, 1998; Fields et al., 2001; Thomas et al., 2005). Similarities among them include virion and DNA size, structure, and genetic organization as well as their replication mechanism that involves reverse transcription of a pregenomic RNA transcript of more than genome length. Phylogenetically, hepadnaviruses, due to similarities in gene number, function, and organization, are related to retroviruses. Hepadnaviruses also show similarities in genetic organization and replication strategy with members of