Immune modulation in chronic hepatitis B patients
(Immuun modulatie in chronische hepatitis B patiënten : een wetenschappelijke proeve op het gebied van de medische wetenschappen)
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The hepatitis B virus (HBV) is a 42 nm viral particle and member of the hepadnaviridae family. Its double-shelled structure consists of an outer envelop composed of surface proteins (HBsAg) and an inner capsid formed by core-proteins (HBcAg) surrounding the partially double stranded DNA (1). The HBV DNA has 4, partially overlapping, open reading frames (ORF's) encoding for the viral antigens. ORF P is the longest one and has four contiguous regions: one encoding for the terminal protein (a covalently bound protein necessary for minus strand syntheses priming (primase)), a second non-specific domain (spacer), a third for the reverse transcriptase and a fourth domain encoding for RNaseH. ORF S encodes for the pre-S1, pre-S2 proteins and the HBs-antigen and is completely located within ORF P. In particular pre-S1 is suggested to be important for viral attachment (2). HBsAg contains the major antigenic a-determinant. HBsAg is produced at the membrane of the endoplasmic reticulum (ER): complete virions, the non-infectious filaments (containing small, middle and large HBsAg proteins) or spheres (consisting of small and middle-sized HBsAg proteins) circulate in serum in excess. ORF C encodes for the (pre-) core proteins, HBeAg and HBcAg. The core particles are postulated to be necessary for the assembly of the virus. HBcAg is synthesized in the cytosol and can be stored in the nucleus. In serum however, it is undetectable in contrast to the secretory form of the core protein, HBeAg. ORF X expresses the X-gene, the putative transcriptional activator of several genes. Both ORF C and ORF X partially overlap with ORF P (1).
This study was performed at the department of Gastroenterology & Hepatology of the University Hospital Rotterdam, The Netherlands. Financial support for this thesis was kindly given by Schering-Piough, GlaxoSmithKiine, Altana Pharma, Bristol-Myers Squibb and AstraZeneca.
- hepatitis b
- combination therapy
- hbv dna
- hbeag seroconversion