Journal of Virology,
Journal Year:
2021,
Volume and Issue:
95(13)
Published: April 19, 2021
YTHDC1
and
fragile
X
mental
retardation
protein
(FMRP)
bind
N6-methyladenosine
(m6A)-modified
RNAs
facilitate
their
transport
to
the
cytoplasm.
Here,
we
investigated
role
of
these
proteins
in
hepatitis
B
virus
(HBV)
gene
expression
life
cycle.
We
have
previously
reported
that
HBV
transcripts
are
m6A
methylated,
this
modification
regulates
viral
is
particularly
interesting,
as
its
DNA
genome
upon
transcription
gives
rise
a
pregenomic
RNA
(pgRNA),
which
serves
template
for
reverse
produce
relaxed
circular
transforms
into
covalently
closed
(cccDNA).
While
negatively
affects
stability
translation
transcripts,
our
current
results
revealed
possibility
it
positively
pgRNA
encapsidation
Thus,
plays
differential
dual
well
FMRP
recognize
m6A-methylated
In
cells
depleted
with
or
FMRP,
accumulate
nucleus
affect
Most
importantly,
core-associated
subsequent
cccDNA
syntheses
dramatically
affected
FMRP-
YTHDC1-silenced
cells.
This
study
highlights
functional
relevance
cycle
potential
arrest
liver
disease
pathogenesis.
IMPORTANCE
been
recently
implicated
nuclear
export
modified
mRNAs.
show
m6A-modified
export.
absence
YTHDC1,
reduce
core
particles
subsequently
synthesis.
Our
shows
how
binding
can
regulate
by
facilitating
RNA.
Antiviral Research,
Journal Year:
2020,
Volume and Issue:
182, P. 104925 - 104925
Published: Aug. 28, 2020
Hepatitis
B
virus
(HBV)
specifically
infects
hepatocytes
and
causes
severe
liver
diseases.
The
HBV
life
cycle
is
unique
in
that
the
genomic
DNA
(relaxed-circular
partially
double-stranded
DNA:
rcDNA)
converted
to
a
molecular
template
(covalently
closed
circular
cccDNA)
amplify
viral
RNA
intermediate,
which
then
reverse-transcribed
back
DNA.
highly
stable
characteristics
of
cccDNA
result
chronic
infection
poor
rate
cure.
This
complex
offers
variety
targets
develop
antiviral
agents.
We
provide
here
an
update
on
current
knowledge
biology
its
cycle,
may
help
identify
new
targets.
Gut,
Journal Year:
2023,
Volume and Issue:
72(5), P. 972 - 983
Published: Jan. 27, 2023
A
major
goal
of
curative
hepatitis
B
virus
(HBV)
treatments
is
the
reduction
or
inactivation
intrahepatic
viral
covalently
closed
circular
DNA
(cccDNA).
Hence,
precise
cccDNA
quantification
essential
in
preclinical
and
clinical
studies.
Southern
blot
(SB)
permits
visualisation
but
lacks
sensitivity
very
laborious.
Quantitative
PCR
(qPCR)
has
no
such
limitations
inaccurate
due
to
codetection
replicative
intermediates
(RI)
can
occur.
The
use
different
samples,
preservation
conditions,
extraction,
nuclease
digestion
methods
qPCR
strategies
hindered
standardisation.
Within
ICE-HBV
consortium,
available
novel
protocols
for
isolation
liver
tissues
cell
cultures
were
compared
six
laboratories
develop
evidence-based
guidance
best
practices.
Journal of Virology,
Journal Year:
2019,
Volume and Issue:
93(20)
Published: July 26, 2019
With
a
yearly
death
toll
of
880,000,
hepatitis
B
virus
(HBV)
remains
major
health
problem
worldwide,
despite
an
effective
prophylactic
vaccine
and
well-tolerated,
antivirals.
HBV
causes
chronic
hepatitis,
fibrosis,
cirrhosis,
hepatocellular
carcinoma.
The
viral
genome
persists
in
infected
hepatocytes
even
after
long-term
antiviral
therapy,
its
integration,
though
no
longer
able
to
support
replication,
destabilizes
the
host
genome.
is
DNA
that
utilizes
virus-encoded
reverse
transcriptase
convert
RNA
intermediate,
termed
pregenomic
RNA,
into
relaxed
circular
genome,
which
subsequently
converted
covalently
closed
(cccDNA)
cell
nucleus.
cccDNA
maintained
nucleus
hepatocyte
as
stable
minichromosome
functions
transcriptional
template
for
production
all
gene
products,
thus,
it
molecular
basis
persistence.
nuclear
pool
can
be
replenished
through
recycling
newly
synthesized,
DNA-containing
capsids.
Licensed
antivirals
target
activity
but
fail
eliminate
cccDNA,
would
required
cure
infection.
Elimination
so
far
only
achieved
by
immune
responses.
Thus,
this
review
will
focus
on
possible
curative
strategies
aimed
at
eliminating
or
crippling
cccDNA.
Newer
insights
life
cycle
response
provide
novel,
potentially
therapeutic
opportunities
targets.
PLoS Pathogens,
Journal Year:
2018,
Volume and Issue:
14(6), P. e1007124 - e1007124
Published: June 21, 2018
Hepatitis
B
virus
(HBV)
is
one
of
the
major
etiological
pathogens
for
liver
cirrhosis
and
hepatocellular
carcinoma.
Chronic
HBV
infection
a
key
factor
in
these
severe
diseases.
During
infection,
forms
nuclear
viral
episome
form
covalently
closed
circular
DNA
(cccDNA).
Current
therapies
are
not
able
to
efficiently
eliminate
cccDNA
from
infected
hepatocytes.
master
template
replication
that
formed
by
conversion
its
precursor,
relaxed
(rcDNA).
However,
host
factors
critical
formation
remain
be
determined.
Here,
we
assessed
whether
potential
factor,
flap
structure-specific
endonuclease
1
(FEN1),
involved
cleavage
flap-like
structure
rcDNA.
In
cell
culture
model
(Hep38.7-Tet),
expression
activity
FEN1
were
reduced
siRNA,
shRNA,
CRISPR/Cas9-mediated
genome
editing,
inhibitor.
These
reductions
did
affect
nucleocapsid
(NC-DNA)
production,
but
reduce
levels
Hep38.7-Tet
cells.
Exogenous
overexpression
wild-type
rescued
production
FEN1-depleted
Anti-FEN1
immunoprecipitation
revealed
binding
DNA.
An
vitro
FEN
assay
demonstrated
5'-flap
synthesized
substrate.
Furthermore,
was
generated
when
purified
rcDNA
incubated
with
recombinant
FEN1,
polymerase,
ligase.
Importantly,
required
assay.
results
demonstrate
system,
ligase
activities
sufficient
convert
into
vitro.
