Figure 1 (A) Atomic resolution rendering of a particle of hepatitis B virus capsid (HBV) (Wynne, S.A., Crowther, R.A. and Leslie, A.G. (1999). Mol. Cell., 3, 771–780). (B) Diagram representing the T=4 structure of an HBV core particle. (C) High resolution cryo-electron micrograph of normal (42–52 nm) isometric virus with icosahedral capsid or “core” surrounded by a coat of HBsAg, and of smaller (ca. 22 nm) spheres and rods composed of viral envelope proteins. The bar represents 65 nm. (Courtesy of B. Boettcher, J. Monjardino and R.A. Crowther.) (Bottom). Negative contrast electron micrographs of HBV virions (left) and virus-associated particles (centre and right), together with an SDS-PAGE protein profile of each particle form to the left of the relevant micrograph. LHBs, MHBs and SHBs refer to large, middle and small HB surface proteins, respectively. HBc, hepatitis B core proteins. GP, glycoprotein; P, protein. The identities of the slower migrating bands are unknown.

(Courtesy of W. Gerlich.)

Figure 2 Genome organization and regulatory elements of orthohepadnaviruses are shown for a typical HBV isolate of genotype A. The outer circle represents the structure of relaxed circular, viral DNA found within virions, while the inner circle illustrates the structure and regulatory elements on cccDNA, the covalently closed circular DNA from which viral mRNAs are transcribed in the nucleus of the infected cell (red = positive strand; blue = negative strand). Numbering starts at the unique EcoRI restriction site located approximately at the junction of the preS1 and preS2 domains in the ORF for the viral envelope proteins. The regulatory elements on the DNA are depicted at their approximate positions. The promoters (P) are shown as grey boxes, and the enhancers (Enh), a glucocorticoid responsive element (GRE), and a CCAAT element (CCAAT) are depicted as black boxes. The basal core promoter is regulated by the negative regulatory element (NRE, not shown), which overlaps with Enh II. Liver-specific promoters are drawn in light grey; non-tissue-specific promoters are depicted as medium grey boxes. The ORFs are drawn as arrows with their corresponding start and termination sites. The viral mRNAs are depicted as black circles in the middle region. The black triangles represent their 5’ ends; the 3’ end is common and linked to an approximately 300 nt polyA tract. The regulatory elements on the RNAs are depicted as a red box (encapsidation signal ɛ), a black box (polyadenylation signal), in pink (DR1), in blue (phi) and in light blue (posttranscriptional regulatory element [PRE]). The genomic DNA is depicted as it is found in the virion. The minus DNA strand is drawn as a blue line with its terminal redundancy (r). The polymerase (green oval) is linked to the 5’ end of the minus strand. The plus-strand DNA is shown as a red line. The dotted red line represents the variation of the 3’ end of the plus strand DNA. The 5’ end of the plus strand is bound to its capped RNA primer, depicted as a black, wavy line. The dotted grey line between the polymerase and the 3’ end of the plus strand DNA reflects the fact that the polymerase is bound to the 5’ end of the minus strand DNA, but interacts with the variable 3’ end of the plus strand DNA for its elongation. The regulatory elements on the minus strand DNA are the DR2 (red box) and the M, 5E and 3E elements, which are required for circularization of the genome. Note that their position and size are approximate, since these elements are not yet completely characterized.

(From Kann, M. (2002). Structure and molecular virology. In: Hepatitis B virus Human Virus Guide. (S. Locarnini and C.L. Lai, Eds.), ch 2. International Medical Press, London; with permission.)

Figure 3 Hepadnavirus replication strategy. For details see text.

Figure 4 Phylogenetic tree of the genus Orthohepadnavirus. Complete genomes of hepatitis B virus (HBV) genotypes A (X02763), B (D00330), C (M12906), D (J02203), E (X75657), F (X69798), G (AF160501) and H (AY090454), and isolates found in chimpanzee (D00220), orangutan (AF193864) and gibbon (U46935), were aligned using Clustal W with orthohepadnavirus genomes from woolly monkey hepatitis B virus (WMHBV) (AF046996), woodchuck hepatitis virus (WHV) (J02442), ground squirrel hepatitis virus (GSHV) (K02715) and Arctic squirrel hepatitis virus (ASHV) (U29144). The alignment was tested with the neighbor-joining method. Calibration bar: substitutions per site.

(Courtesy of Schaefer.)