Epatite Cronica B
Il Virus
Giovanni Raimondo
U.O.C. EpatologiaClinica e Biomolecolare
A.O.U. Policlinico G. Martino Messina
Giovanni Raimondo
HBV: Il Virus
Il sottoscritto dichiara di non aver avuto negli ultimi 12 mesi conflitto d’interesse in relazione a questa presentazione
e
che la presentazione non contiene discussione di farmaci in studio o ad uso off-label
HBV GENOME
S gene: pre S1(large S), preS2 (middle S), S (small S)
X gene: X
Core gene: core, e
Pol gene: P
H
E
P
A
T
I
T
I
S
B V
I
R
U
S
H
E
P
A
T
I
T
I
S
B V
I
R
U
S
nucleus citoplasm
repair
mRNA transcription
Core particle plus strand syntesis
mRNA transport
translationRibosome
Transport to cell membrane
HBV
preCore
HBXSecreted HBeAg
ER
Spheres and Filamentes containing HBsAg
Small HBsMedium HBsLarge HBs
Envelope
Subgenomic and Geneomic RNA
Pre-genomic RNACorePol
cccDNA
Golgi complex
Entry of HBV into cell and uncoating
Core particle minus strand syntesis
Core assembly and RNA packaging
HBV life cycle
RECYCLING
Visualization of HBV integration breakpoints in the HCC and HBV genomes.
HEPATITIS B VIRUS Genome Organization
• 3.2 kb pdDNA• 3 promoters = Core, S-, and X• 4 ORF = preC/Core, pre-S1/pre-
S2/S, Polymerase, X-gene
HBV open reading frames
* aa 108/119
according to genotype
*
modified from Warner and Locarnini
Modified from Chan H L-Y et al, J Hepatol 2011
HBVwt HBV172* HBVwt + HBV172* mix
Warner, N and Locarnini, S. Hepatology 2008.
preS1 mutant HBV Wild type HBV
Pollicino et al, Hepatology 2012
Cancer Sci. 2006 Aug;97(8):683-8.
Distribution of preS2-defective variants in
HBsAg+ patients (pts)¶ with difefrent clinical pictures
Raimondo et al, J hepatol 2004
Diagnosis
Inactive Carriers°
Chronic hepatitis°*
Cirrhosis°*
HCC°*
N° pts
15
50
26
19
N° pS2 variants
2
25
13
16
°p=0.002
*p=0.02
¶ All pts infected with genotype D
Prevalence of pre-S mutants in patients infected with genotype
B, C, or mixed genotypesChen F-B et al, Gastroenterology 2006
cc : chronic (inactive) carriers
CH : chronic hepatitis
LC : liver cirrhosis
Deletion
Wild-type + deletion
Wild-type
The two separate pathways of HBsAg and HBVDNA production
Nguyen T, J Hepatol 2010
HBsAg secretory pathway and the viral replication pathway
are distinct within the hepatocyte
Geographic Distributionof HBV Genotypes
Genotype A : World-wide
“ “ B : Asia
“ “ C : Asia
“ “ D : South Europe, Americas, Australia
“ “ E : Africa
“ “ F : Native Americans and Polynesians
“ “ G : Europe, U.S.A.
“ “ H : Native Americans
Chimpanzee
Gibbon
Orang-Utan
Woolly monkey
T--C--
--T
CC-
-C--A-
--A-G-
ATG
1839
Insertion
Deletion
DR1 RNA encapsidation signal
X gene
TAA TAG
1817CAA
1874 1896 1897
AAG TGG
TAG
1838/9
pre-C ATG C ATG
B
A
TGA
pre-C pregenome/C mRNA
1899/1900
pre-C region/precore protein
1814-6
Pre-C mutations preventing HBeAg synthesis
Pre-C C P
X1374 1836
1591 1850Enhancer II/core promoter region
1762A T
1764G A
Core Promoter Mutations
Saint Jerome
Antonello da Messina
London, National Gallery
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