Cell Reports,
Journal Year:
2013,
Volume and Issue:
4(6), P. 1108 - 1115
Published: Sept. 1, 2013
Long
interspersed
elements
1
(LINE-1)
occupy
at
least
17%
of
the
human
genome
and
are
its
only
active
autonomous
retrotransposons.
However,
host
factors
that
regulate
LINE-1
retrotransposition
not
fully
understood.
Here,
we
demonstrate
Aicardi-Goutières
syndrome
gene
product
SAMHD1,
recently
revealed
to
be
an
inhibitor
HIV/simian
immunodeficiency
virus
(SIV)
infectivity
neutralized
by
viral
Vpx
protein,
is
also
a
potent
regulator
LINE-1-mediated
Alu/SVA
retrotransposition.
We
found
mutant
SAMHD1s
patients
defective
in
inhibition.
Several
domains
SAMHD1
critical
for
regulation.
inhibits
dividing
cells.
An
enzymatic
site
maintained
substantial
anti-LINE-1
activity.
ORF2p-mediated
reverse
transcription
isolated
ribonucleoproteins
reducing
ORF2p
level.
Thus,
may
cellular
activity
conserved
mammals.
Science,
Journal Year:
2013,
Volume and Issue:
343(6169), P. 428 - 432
Published: Dec. 20, 2013
The
progressive
depletion
of
quiescent
“bystander”
CD4
T
cells,
which
are
nonpermissive
to
HIV
infection,
is
a
principal
driver
the
acquired
immunodeficiency
syndrome
(AIDS).
These
cells
undergo
abortive
infection
characterized
by
cytosolic
accumulation
incomplete
reverse
transcripts.
viral
DNAs
sensed
an
unidentified
host
sensor
that
triggers
innate
immune
response,
leading
caspase-1
activation
and
pyroptosis.
Using
unbiased
proteomic
targeted
biochemical
approaches,
as
well
two
independent
methods
lentiviral
short
hairpin
RNA–mediated
gene
knockdown
in
primary
we
identify
interferon-γ–inducible
protein
16
(IFI16)
DNA
required
for
cell
death
due
infection.
findings
provide
insights
into
key
pathway
plays
central
role
during
disease
progression
AIDS.
Mobile DNA,
Journal Year:
2016,
Volume and Issue:
7(1)
Published: Aug. 11, 2016
Retrotransposons
have
generated
about
40
%
of
the
human
genome.
This
review
examines
strategies
cell
has
evolved
to
coexist
with
these
genomic
"parasites",
focussing
on
non-long
terminal
repeat
retrotransposons
humans
and
mice.
Some
restriction
factors
for
retrotransposition,
including
APOBECs,
MOV10,
RNASEL,
SAMHD1,
TREX1,
ZAP,
also
limit
replication
retroviruses,
HIV,
are
part
intrinsic
immune
system
cell.
Many
proteins
act
in
cytoplasm
degrade
retroelement
RNA
or
inhibit
its
translation.
nucleus
involve
DNA
repair
enzymes
epigenetic
processes
methylation
histone
modification.
RISC
piRNA
pathway
protect
germline.
Retrotransposon
control
is
relaxed
some
types,
such
as
neurons
brain,
stem
cells,
certain
types
disease
cancer,
implications
health
disease.
considers
potential
pitfalls
interpreting
retrotransposon-related
data,
well
issues
consider
future
research.
Cell Reports,
Journal Year:
2013,
Volume and Issue:
3(4), P. 1036 - 1043
Published: April 1, 2013
SAMHD1
restricts
HIV-1
replication
in
myeloid
and
quiescent
CD4+
T
cells.
Here,
we
show
that
restriction
activity
is
regulated
by
phosphorylation.
interacts
with
cyclin
A2/cdk1
only
cycling
Cyclin
A2/CDK1
phosphorylates
at
the
Threonine
592
residue
both
vitro
vivo.
Phosphorylation
of
Thr592
correlates
loss
its
ability
to
restrict
HIV-1.
Indeed,
while
PMA
treatment
proliferating
THP1
cells
results
reduced
phosphorylation,
activation
resting
peripheral
blood
mononuclear
(PBMCs)
purified
increased
phosphorylation
Thr592.
Interestingly,
found
type
1
interferon
reinforcing
link
between
antiviral
activity.
Unlike
wild-type
SAMHD1,
a
phosphorylation-defective
mutant
was
able
PMA-treated
untreated
Our
uncover
as
key
regulatory
mechanism
Retrovirology,
Journal Year:
2013,
Volume and Issue:
10(1)
Published: June 26, 2013
Combination
antiretroviral
therapy,
despite
being
potent
and
life-prolonging,
is
not
curative
does
eradicate
HIV-1
infection
since
interruption
of
treatment
inevitably
results
in
a
rapid
rebound
viremia.
Reactivation
latently
infected
cells
harboring
transcriptionally
silent
but
replication-competent
proviruses
potential
source
persistent
residual
viremia
cART-treated
patients.
Although
multiple
reservoirs
may
exist,
the
persistence
resting
CD4+
T
carrying
latent
represents
major
barrier
to
eradication.
In
this
review,
we
will
discuss
latest
reports
on
molecular
mechanisms
that
regulate
latency
at
transcriptional
level,
including
interference,
role
cellular
factors,
chromatin
organization
epigenetic
modifications,
viral
Tat
trans-activator
its
cofactors.
Since
also
operate
post-transcriptional
consider
inhibition
nuclear
RNA
export
translation
by
microRNAs
as
barriers
gene
expression.
Finally,
review
therapeutic
approaches
clinical
studies
aimed
achieving
either
sterilizing
cure
or
functional
infection,
with
special
emphasis
most
recent
pharmacological
strategies
reactivate
viruses
decrease
pool
reservoirs.
