Viral Description & Life Cycle

Hepatitis B virus (HBV) is a DNA virus of the hepadnaviridae family. The HBV
virion, also called a Dane particle, is approximately 42 nm in diameter and consists of
an inner protein core and an outer protein envelope. The outer envelope is composed
of several proteins, known as hepatitis B surface proteins (HBs), which encase the
nucleocapsid, or inner protein shell, made of hepatitis B core proteins (HBc) (Bruss
and Ganem, 1991). The nucleocapsid is arranged into an icosahedral formation and
contains the hepatitis B genome and at least one hepatitis B polymerase protein. The
figure below shows a diagram of the DNA virus.

Figure 3. Image from http://www.hon.ch/Library/Theme/HepB/hbvirus.GIF
The viral genome is circular and is characterized by regions that are composed of
single, double, and triple-stranded DNA. Within the genome are four partially
overlapping open reading frames (ORFs) that encode seven different HBV genes,
including but not limited to the hepatitis B surface antigen gene, also called the S
gene, the hepatitis B core antigen gene, known as the C gene, the X gene, and the
polymerase (P) gene (Ocama et. al., 2005). The figure below shows an image of the
viral genome.

Figure 4. Image from http://www.scielo.br/img/revistas/rhc/v59n4/21391f1.gif
Unlike other envelope proteins, HBs span the lipid bilayer multiple times. There are
three different size proteins based on the reading frame, yielding small, medium, and
large HBs. The large hepatitis B surface antigen is believed to be most responsible for
conducting viral-host cell attachment. A specific receptor, however, has yet to be
identified. Another unique feature is that HBs can be secreted as subviral particles,
lacking all other parts of the virion. Such particles are termed hepatitis B filaments
and hepatitis B spheres, each of which has a diameter of 22nm. Increased levels can
be found during acute infection. However, because these particles lack core proteins,
polymerase, and viral DNA, they are non-infectious and do not appear to be
advantageous to the virus (Bruss and Ganem, 1991).

Once the virus enters the body of a host, it infects liver cells. In doing so, the viral
surface proteins fuse with the host cell membrane, allowing the core particle to enter
the liver cell. Although early steps in viral entry are not clearly defined, the uncoated
particle (or nucleocapsid) is transported into the nuclear membrane of the host cell.
The viral DNA is then brought into the nucleus and is repaired to form a covalently
closed-circular form, known as cccDNA. Viral DNA is not integrated into the host
DNA like some viruses. Instead, once the DNA is recircularized, transcription of viral
DNA and proteins begins and is controlled by four promoter elements and two
enhancer elements. DNA polymerase then begins copying the DNA. The polymerase
protein uses its unique shape to initiate reverse transcription and copy the DNA.
Unlike retroviruses, hepadnaviruses bind polymerase proteins into a stem-loop
formation, which are subsequently packaged by core proteins in the golgi and secreted
via exocytosis into the blood stream, where it can contact other liver cells and
continue replication (Rehermann and Michelina, 2005).

Figure 5. Image from http://mgl.snu.ac.kr/images/HBV%20life%20cycle.jpg

Bruss, V. & Ganem, D. 1991. The role of envelope proteins in hepatitis B virus
assembly. Proceedings of the National Academy of Science USA 88:1059-1063.
Ocama, P., Opio, C., & Lee, W. 2005. Hepatitis B virus infection: Current status. The
American Journal of Medicine. 118(12):1413-1420.
Rehermann, B. and Nascimbeni, M. 2005. Immunology of hepatitis B virus and
hepatitis C virus infection. Immunology 5: 215-229.


Return to Christie's Immunology Home Page
Christie Brough. Biology 307: Immunology. Dr. S. Sarafova. Davidson College. May
4, 2007.