The art of hijacking: how Nsp1 impacts host gene expression during coronaviral infections
Biochemical Society Transactions,
Год журнала:
2024,
Номер
52(1), С. 481 - 490
Опубликована: Фев. 22, 2024
Non-structural
protein
1
(Nsp1)
is
one
of
the
first
proteins
produced
during
coronaviral
infections.
It
plays
a
pivotal
role
in
hijacking
and
rendering
host
gene
expression
under
service
virus.
With
focus
on
SARS-CoV-2,
this
review
presents
how
Nsp1
selectively
inhibits
synthesis
induces
mRNA
degradation
but
not
viral
mRNAs
blocks
nuclear
export.
The
clinical
implications
are
highlighted
by
showcasing
pathogenic
through
repression
interferon
pathways
features
variants
with
mutations
coding
sequence.
ability
SARS-CoV-2
to
hinder
immune
responses
at
an
early
step,
absence
homology
any
human
proteins,
availability
structural
information
render
ideal
drug
target
therapeutic
potential.
Язык: Английский
Betacoronaviruses Differentially Activate the Integrated Stress Response to Optimize Viral Replication in Lung-Derived Cell Lines
Viruses,
Год журнала:
2025,
Номер
17(1), С. 120 - 120
Опубликована: Янв. 16, 2025
The
betacoronavirus
genus
contains
five
of
the
seven
human
coronaviruses,
making
it
a
particularly
critical
area
research
to
prepare
for
future
viral
emergence.
We
utilized
three
betacoronaviruses,
one
from
each
subgenus—HCoV-OC43
(embecovirus),
SARS-CoV-2
(sarbecovirus),
and
MERS-CoV
(merbecovirus)—,
study
interactions
with
PKR-like
ER
kinase
(PERK)
pathway
integrated
stress
response
(ISR)/unfolded
protein
(UPR).
PERK
becomes
activated
by
an
abundance
unfolded
proteins
within
endoplasmic
reticulum
(ER),
leading
phosphorylation
eIF2α
translational
attenuation.
demonstrate
that
MERS-CoV,
HCoV-OC43,
all
activate
induce
responses
downstream
p-eIF2α,
while
only
induces
detectable
p-eIF2α
during
infection.
Using
small
molecule
inhibitor
dephosphorylation,
we
provide
evidence
HCoV-OC43
maximize
replication
through
dephosphorylation.
Interestingly,
genetic
ablation
growth
arrest
DNA
damage-inducible
(GADD34)
expression,
inducible
phosphatase
1
(PP1)-interacting
partner
targeting
did
not
significantly
alter
or
replication,
siRNA
knockdown
constitutive
PP1
partner,
repressor
(CReP),
dramatically
reduced
replication.
Combining
GADD34
knockout
CReP
had
maximum
impact
on
was
unaffected.
Overall,
conclude
dephosphorylation
is
efficient
production
SARS-CoV-2,
however,
appears
be
insensitive
and,
infection,
may
even
downregulate
limit
host
translation.
Язык: Английский
The transcriptional and translational landscape of HCoV-OC43 infection
PLoS Pathogens,
Год журнала:
2025,
Номер
21(1), С. e1012831 - e1012831
Опубликована: Янв. 27, 2025
The
coronavirus
HCoV-OC43
circulates
continuously
in
the
human
population
and
is
a
frequent
cause
of
common
cold.
Here,
we
generated
high-resolution
atlas
transcriptional
translational
landscape
OC43
during
time
course
following
infection
lung
fibroblasts.
Using
ribosome
profiling,
quantified
relative
expression
canonical
open
reading
frames
(ORFs)
identified
previously
unannotated
ORFs.
These
included
several
potential
short
upstream
ORFs
putative
ORF
nested
inside
M
gene.
In
parallel,
analyzed
cellular
response
to
infection.
Endoplasmic
reticulum
(ER)
stress
genes
were
transcriptionally
translationally
induced
beginning
12
18
hours
post
infection,
respectively.
By
contrast,
conventional
antiviral
mostly
remained
quiescent.
At
same
points,
observed
accumulation
increased
translation
noncoding
transcripts
normally
targeted
by
nonsense
mediated
decay
(NMD),
suggesting
NMD
suppressed
This
work
provides
resources
for
deeper
understanding
gene
responses
Язык: Английский
SARS-CoV-2 Nsp1-Resistant Modified RNA for the Creation of Nsp1-Responsive Systems
ACS Synthetic Biology,
Год журнала:
2025,
Номер
unknown
Опубликована: Июнь 5, 2025
Modified
RNA
(modRNA)
facilitates
the
introduction
of
complex
synthetic
genetic
circuits
into
cells
without
risk
genomic
integration,
opening
up
implementation
as
therapeutics.
However,
number
protein-RNA
interfaces
that
are
suitable
for
construction
protein-responsive
modRNA
switches
well
lack
exclusive
selector
systems
stifles
development
RNA-based
circuits.
Here,
we
present
creation
a
capable
resisting
effects
Nsp1
reliable
expression
its
coding
sequence.
Using
both
subgenomic
viral
5'UTR
and
two
modified
nucleosides,
observed
efficient
exogenous
protein
even
in
Nsp1-transfected
cells.
To
demonstrate
utility,
developed
barnase-barstar
system
conditional
transcript
suppression
presence
Nsp1.
Altogether,
resistance
to
Nsp1-mediated
translational
resulting
Nsp1-sensing
this
study
provide
an
invaluable
opportunity
develop
new
class
protein-sensing
more
Язык: Английский
SARS-CoV-2 Nsp1 traps RNA in the nucleus to escape immune detection
Proceedings of the National Academy of Sciences,
Год журнала:
2024,
Номер
121(25)
Опубликована: Июнь 6, 2024
Язык: Английский
Betacoronaviruses Differentially Activate the Integrated Stress Response to Optimize Viral Replication in Lung Derived Cell Lines
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Сен. 26, 2024
The
betacoronavirus
genus
contains
five
of
the
seven
human
viruses,
making
it
a
particularly
critical
area
research
to
prepare
for
future
viral
emergence.
We
utilized
three
betacoronaviruses,
one
from
each
subgenus-HCoV-OC43
(embecovirus),
SARS-CoV-2
(sarbecovirus)
and
MERS-CoV
(merbecovirus)-
study
interaction
with
PKR-like
ER
kinase
(PERK)
pathway
integrated
stress
response
(ISR)/unfolded
protein
(UPR).
PERK
becomes
activated
by
an
abundance
unfolded
proteins
within
endoplasmic
reticulum
(ER),
leading
phosphorylation
eIF2α
translational
attenuation
in
lung
derived
cell
lines.
demonstrate
that
MERS-CoV,
HCoV-OC43,
all
activate
induce
responses
downstream
p-eIF2α,
while
only
induces
detectable
p-eIF2α
during
infection.
Using
small
molecule
inhibitor
dephosphorylation,
we
provide
evidence
HCoV-OC43
maximize
replication
through
dephosphorylation.
Interestingly,
genetic
ablation
GADD34
expression,
inducible
phosphatase
1
(PP1)-interacting
partner
targeting
did
not
significantly
alter
or
replication,
siRNA
knockdown
constitutive
PP1
partner,
CReP,
dramatically
reduced
replication.
Combining
growth
arrest
DNA
damage-inducible
(GADD34)
knockout
peripheral
membrane-targeted
(CReP)
had
maximum
impact
on
was
unaffected.
Overall,
conclude
dephosphorylation
is
efficient
production
SARS-CoV-2,
however,
appears
be
insensitive
and,
infection,
may
even
downregulate
limit
host
translation.
Язык: Английский
4D-DIA-Based Quantitative Proteomic Analysis Reveals the Involvement of TRPV2 Protein in Duck Tembusu Virus Replication
Viruses,
Год журнала:
2024,
Номер
16(12), С. 1831 - 1831
Опубликована: Ноя. 26, 2024
Duck
Tembusu
virus
(DTMUV),
a
novel
positive-sense
RNA
virus,
has
caused
significant
economic
losses
in
the
poultry
industry
of
Eastern
and
Southeast
Asia
since
its
outbreak
2010.
Furthermore,
rapid
transmission
potential
zoonotic
nature
DTMUV
pose
threat
to
public
health
safety.
In
this
study,
4D-DIA
quantitative
proteomics
approach
was
employed
identify
differentially
expressed
cellular
proteins
DTMUV-infected
DF-1
cells,
which
are
routinely
used
for
isolation
identification
DTMUV,
as
well
development
vaccines
against
other
viruses.
One
hundred
fifty-seven
were
identified,
including
84
upregulated
73
downregulated
at
48
h
post-infection,
among
CXCL8,
DDX3X,
TRPV2
may
play
crucial
roles
viral
propagation.
Notably,
protein
TRPV2,
replication
inhibited
TRPV2-low-expressing
cells.
summary,
our
research
represents
application
analyze
proteomic
landscape
These
findings
provide
valuable
insights
into
understanding
interaction
mechanism
between
disease-resistant
host
factors
breeding
research.
Язык: Английский