Hepatitis B virus infection: Is patient tailored treatment feasible?
The hepatitis B virus (HBV) belongs to the family of hepadna viridae and has a diameter of 42-47 nm. The virus particle encloses a partially double-stranded DNA genome with a length of approximately 3200 base pairs. Within the viral DNA genome four open reading frames (ORFs) can be identified and are termed in analogy of their encoding protein S (surface), C (core), P (polymerase) and X (HBx protein). The ORF S contains 3 regions, the ore S1, pre S2 and S, which encode for the large, middle and small hepatitis B surface glycoproteins depending on the start of the transcription site, respectively. The ORF C is responsible for encoding the hepatitis B e-antigen (HBeAg) and the core antigen (HBcAg). After the binding of the virus particle to the hepatocyte, the HBV viral genome is converted into covalently closed circular DNA (cccDNA) in the hepatocyte nucleus. This cccDNA form the key template for pregenomic RNA in the HBV replication cycle and acts as a reservoir for the HBV. In the hepatocyte cytoplasm, along with the core and polymerase proteins the pregenomic RNA is assembled to virus particles. Sequentially, the RNA is reversed transcribed into a HBV-DNA minus strand, which is finally transcribed by a HBV DNA polymerase into the HBV DNA plus strand. The formed particle can either be excreted via the Golgi apparatus or recycled into the nucleus to form ccc-DNA. As a result of variety in expression of the viral genome, the HBV is divided into 8 different genotypes, A-H. The HBV genotypes are also characterized by different geographical and demographical distribution. Genotype A is predominantly found in North-West Europe and North America, whereas genotypes B and C are mostly seen in Asian countries. Genotype D is most common in the Mediterranean area. Consequently, Caucasians harbor predominantly genotype A and D, while Asians harbor almost exclusively the genotypes B and C. Hepatitis B virus infection is a serious global health problem with more than 350 million people suffering from chronic hepatitis B virus infection.
|Keywords||Hepatitis B, gastroenterology, infectious diseases, liver diseases|
|Promotor||Janssen, H.L.A. (Harry)|
|Publisher||Erasmus MC: University Medical Center Rotterdam|
Leemans, W.F.. (2008, December 19). Hepatitis B virus infection: Is patient tailored treatment feasible? . Erasmus MC: University Medical Center Rotterdam. Retrieved from http://hdl.handle.net/1765/38094