Disparate macrophage responses are linked to infection outcome of Hantan virus in humans or rodents
Hongwei Ma,
No information about this author
Yongheng Yang,
No information about this author
Tiejian Nie
No information about this author
et al.
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Jan. 10, 2024
Abstract
Hantaan
virus
(HTNV)
is
asymptomatically
carried
by
rodents,
yet
causes
lethal
hemorrhagic
fever
with
renal
syndrome
in
humans,
the
underlying
mechanisms
of
which
remain
to
be
elucidated.
Here,
we
show
that
differential
macrophage
responses
may
determine
disparate
infection
outcomes.
In
mice,
late-phase
inactivation
inflammatory
prevents
cytokine
storm
usually
occurs
HTNV-infected
patients.
This
attained
elaborate
crosstalk
between
Notch
and
NF-κB
pathways.
Mechanistically,
receptors
activated
HTNV
enhance
signaling
recruiting
IKKβ
p65,
promoting
polarization
both
species.
However,
mice
rather
than
Notch-mediated
inflammation
timely
restrained
a
series
murine-specific
long
noncoding
RNAs
transcribed
pathway
negative
feedback
manner.
Among
them,
lnc-ip65
detaches
p65
from
receptor
inhibits
phosphorylation,
rewiring
macrophages
pro-inflammation
pro-resolution
phenotype.
Genetic
ablation
leads
destructive
mice.
Thus,
our
findings
reveal
an
immune-braking
function
murine
RNAs,
offering
special
therapeutic
strategy
for
infection.
Language: Английский
UBR5 promotes antiviral immunity by disengaging the transcriptional brake on RIG-I like receptors
Nature Communications,
Journal Year:
2024,
Volume and Issue:
15(1)
Published: Jan. 26, 2024
Abstract
The
Retinoic
acid-Inducible
Gene
I
(RIG-I)
like
receptors
(RLRs)
are
the
major
viral
RNA
sensors
essential
for
initiation
of
antiviral
immune
responses.
RLRs
subjected
to
stringent
transcriptional
and
posttranslational
regulations,
which
ubiquitination
is
one
most
important.
However,
role
in
RLR
transcription
unknown.
Here,
we
screen
375
definite
ubiquitin
ligase
knockout
cell
lines
identify
Ubiquitin
Protein
Ligase
E3
Component
N-Recognin
5
(UBR5)
as
a
positive
regulator
transcription.
UBR5
deficiency
reduces
responses
viruses,
while
increases
replication
primary
cells
mice.
Ubr5
mice
more
susceptible
lethal
virus
infection
than
wild
type
littermates.
Mechanistically,
mediates
Lysine
63-linked
Tripartite
Motif
28
(TRIM28),
an
epigenetic
repressor
RLRs.
This
modification
prevents
intramolecular
SUMOylation
TRIM28,
thus
disengages
TRIM28-imposed
brake
on
In
sum,
enables
rapid
upregulation
expression
boost
by
ubiquitinating
de-SUMOylating
TRIM28.
Language: Английский
A Novel pH‐Responsive Baicalein@Chitosan Hydrogel for the Topical Treatment of Herpes Simplex Virus Type 1 Skin Infections: Therapeutic Potential and Mechanisms
Yu-Hui Lu,
No information about this author
Li-Ying Zhou,
No information about this author
A. Ouyang
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et al.
Advanced Healthcare Materials,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 20, 2025
Abstract
Herpes
simplex
virus
type
1
(HSV‐1)
is
a
prevalent
human
pathogen
primarily
transmitted
through
skin‐to‐skin
contact.
Traditional
antiviral
drugs
like
acyclovir
(ACV)
have
limitations
due
to
viral
resistance
and
side
effects,
necessitating
the
development
of
alternative
therapeutic
strategies.
Drug‐loaded
hydrogels
emerged
as
promising
approach
for
managing
various
skin
infections.
Considering
low‐pH
microenvironment
following
HSV‐1
infection,
pH‐responsive
baicalein@chitosan
(B@C)
hydrogel
developed
topical
treatment
This
synthesized
by
incorporating
baicalein,
natural
flavonoid,
into
chitosan
matrix
modified
with
4‐formylphenylboronic
acid
protocatechualdehyde
achieve
potent
anti‐HSV‐1
activity
pH‐responsiveness.
In
vitro
results
demonstrated
hydrogel's
pH‐dependent
inhibitory
effect
on
infections,
including
ACV‐resistant
strains.
Subsequent
investigations
confirmed
its
efficacy
in
multiple
murine
infection
models.
Mechanistically,
B@C
inhibited
replication
modulating
phosphorylation
inhibitor
nuclear
factor
kappa‐B
kinase
subunit
beta,
promoted
collagen
synthesis,
decreased
reactive
oxygen
species
generation.
Ultra‐high‐performance
liquid
chromatography‐tandem
mass
spectrometry
analysis
revealed
sustained
release
baicalein
from
hydrogel,
ensuring
long‐term
drug
retention
HSV‐1‐infected
tissues.
Collectively,
these
findings
suggest
that
holds
significant
potential
management
Language: Английский
Goose IFIT5 positively regulates goose astrovirus replication in GEF cells
Ruixue Li,
No information about this author
Saimin Zhai,
No information about this author
Shenyan Gao
No information about this author
et al.
Poultry Science,
Journal Year:
2024,
Volume and Issue:
103(8), P. 103930 - 103930
Published: June 1, 2024
Interferon-induced
protein
with
tetratricopeptide
repeats
(IFITs),
a
family
of
proteins
strongly
induced
by
type
I
interferon
(IFN-I),
are
deeply
involved
in
many
cellular
and
viral
processes.
IFIT5,
the
sole
this
found
birds,
also
plays
crucial
role
regulating
virus
infection.
In
study,
goose
IFIT5
(gIFIT5)
was
first
cloned
from
peripheral
blood
lymphocyte
(PBL)
phylogenetic
analysis
showed
that
it
highly
homologous
duck
(dIFIT5),
sharing
94.6%
identity
amino
acid
sequence.
Subsequently,
expression
kinetics
gIFIT5
during
astrovirus
(GAstV)
infection
regulatory
effect
on
GAstV
proliferation
were
evaluated.
Results
mRNA
level
greatly
infection,
especially
at
12
hpi.
Importantly,
could
conversely
promote
replication
GEF
cells.
Virus
titers
overexpression
group
significantly
higher
than
those
control
24
Western
blot
quantitative
real-time
PCR
(qRT-PCR)
further
demonstrated
production
cap
facilitated
gIFIT5-transfected
group.
Collectively,
facilitates
self-replication
via
promoting
expression.
Language: Английский
Mouse guanylate‐binding protein 1 does not mediate antiviral activity against influenza virus in vitro or in vivo
Immunology and Cell Biology,
Journal Year:
2023,
Volume and Issue:
101(5), P. 383 - 396
Published: Feb. 6, 2023
Abstract
Many
interferon
(IFN)‐stimulated
genes
are
upregulated
within
host
cells
following
infection
with
influenza
and
other
viruses.
While
the
antiviral
activity
of
some
IFN‐stimulated
genes,
such
as
IFN‐inducible
GTPase
myxoma
resistance
(Mx)1
protein
1,
has
been
well
defined,
less
is
known
regarding
activities
related
GTPases
guanylate‐binding
(GBP)
family,
particularly
mouse
GBPs,
where
models
can
be
used
to
assess
their
properties
in
vivo
.
Herein,
we
demonstrate
that
GBP1
(mGBP1)
was
a
airway
epithelial
cell
line
(LA‐4
cells)
pretreatment
IFNα
or
by
A
virus
(IAV).
Whereas
doxycycline‐inducible
expression
Mx1
(mMx1)
LA‐4
resulted
reduced
susceptibility
IAV
viral
growth,
inducible
mGBP1
did
not.
Moreover,
primary
isolated
from
mGBP1‐deficient
mice
(mGBP1
−/−
)
showed
no
difference
macrophages
defect
IAV‐induced
NLRP3
(NLR
family
pyrin
domain
containing
3)
inflammasome
activation.
After
intranasal
infection,
also
differences
replication
induction
inflammatory
responses
airways
during
infection.
Thus,
using
complementary
approaches
overexpression,
does
not
play
major
role
modulating
vitro
Language: Английский
TRIM16 Overexpression in HEK293T Cells Results in Cell Line-Specific Antiviral Activity
Pathogens,
Journal Year:
2023,
Volume and Issue:
12(6), P. 852 - 852
Published: June 20, 2023
Host
cell
restriction
factors
are
intracellular
proteins
that
can
inhibit
virus
replication.
Characterisation
of
novel
host
provide
potential
targets
for
host-directed
therapies.
In
this
study,
we
aimed
to
assess
a
member
the
Tripartite-motif
family
protein
(TRIM)
family,
TRIM16,
as
putative
factor.
To
end,
utilized
constitutive
or
doxycycline-inducible
systems
overexpress
TRIM16
in
HEK293T
epithelial
cells
and
then
tested
its
ability
growth
by
range
RNA
DNA
viruses.
cells,
overexpression
resulted
potent
inhibition
multiple
viruses,
however,
when
was
overexpressed
other
lines
(A549,
Hela,
Hep2),
not
observed.
When
investigating
antiviral
activity
endogenous
report
siRNA-mediated
knockdown
A549
also
modulated
mRNA
expression
TRIM
proteins,
complicating
interpretation
results
using
method.
Therefore,
used
CRISPR/Cas9
editing
knockout
demonstrate
did
mediate
against
viruses
tested.
Thus,
while
initial
suggested
factor,
alternative
approaches
validate
these
findings.
These
studies
highlight
importance
complementary
experimental
approaches,
including
analysis
investigation
protein,
defining
with
activity.
Language: Английский
Expression of a Functional Mx1 Protein Is Essential for the Ability of RIG-I Agonist Prophylaxis to Provide Potent and Long-Lasting Protection in a Mouse Model of Influenza A Virus Infection
Lara S. U. Schwab,
No information about this author
Fernando Villalón‐Letelier,
No information about this author
Melkamu B. Tessema
No information about this author
et al.
Viruses,
Journal Year:
2022,
Volume and Issue:
14(7), P. 1547 - 1547
Published: July 15, 2022
RIG-I
is
an
innate
sensor
of
RNA
virus
infection
and
its
activation
induces
interferon-stimulated
genes
(ISGs).
In
vitro
studies
using
human
cells
have
demonstrated
the
ability
synthetic
agonists
(3pRNA)
to
inhibit
IAV
replication.
However,
in
mouse
models
effectiveness
3pRNA
reported
date
differs
markedly
between
studies.
Myxoma
resistance
(Mx)1
ISG
protein
which
mediates
potent
anti-IAV
activity,
however
most
inbred
strains
do
not
express
a
functional
Mx1.
Herein,
we
utilised
C57BL/6
mice
that
(B6.A2G-Mx1)
(B6-WT)
Mx1
assess
prophylactic
treatment
induce
ISGs
protect
against
subsequent
infection.
vitro,
primary
lung
from
B6-WT
B6.A2G-Mx1
resulted
induction
inhibition
was
more
mice.
vivo,
single
intravenous
injection
lungs
both
mice,
long-lasting
protection
challenge
only
observed
Thus,
despite
broad
induction,
expression
critical
for
agonist-mediated
model
Language: Английский
Mouse guanylate-binding proteins of the chromosome 3 cluster do not mediate antiviral activity in vitro or in mouse models of infection
Communications Biology,
Journal Year:
2024,
Volume and Issue:
7(1)
Published: Aug. 25, 2024
Dynamin-like
GTPase
proteins,
including
myxoma
(Mx)
and
guanylate-binding
proteins
(GBPs),
are
among
the
many
interferon
stimulated
genes
induced
following
viral
infections.
While
studies
report
that
human
(h)GBPs
inhibit
different
viruses
in
vitro,
few
have
convincingly
demonstrated
mouse
(m)GBPs
mediate
antiviral
activity,
although
mGBP-deficient
mice
been
used
extensively
to
define
their
importance
immunity
diverse
intracellular
bacteria
protozoa.
Herein,
we
demonstrate
individual
(overexpression)
or
collective
(knockout
(KO)
mice)
mGBPs
of
chromosome
3
cluster
(mGBPchr3)
do
not
replication
five
from
virus
families
nor
observe
differences
titres
recovered
wild
type
versus
mGBPchr3
KO
after
infection
with
three
these
(influenza
A
virus,
herpes
simplex
1
lymphocytic
choriomeningitis
virus).
These
data
indicate
appear
be
a
major
component
cell-intrinsic
against
tested
our
studies.
Mouse
guanylate
binding
potent
activity
vitro
vivo.
Language: Английский
Regulatory pathway underpinning the development of encephalitis after simian immunodeficiency virus infection in rhesus macaques (Macaca mulatta)
Taeho Kwon,
No information about this author
Hong‐Yi Xiang,
No information about this author
Xiao‐Ya Xing
No information about this author
et al.
Journal of Medical Primatology,
Journal Year:
2023,
Volume and Issue:
52(4), P. 259 - 271
Published: June 5, 2023
Abstract
Background
Simian
immunodeficiency
virus
(SIV)
infection
in
rhesus
macaques
(
Macaca
mulatta
)
can
lead
to
the
development
of
SIV
encephalitis
(SIVE),
which
is
closely
related
human
(HIV)‐induced
dementia.
Methods
This
was
done
by
analyzing
and
SIVE
infected
M.
hippocampus
samples
from
two
microarray
data
sets,
identifying
groups
common
differentially
expressed
genes
predicting
associated
protein
interactions.
Results
We
found
that
eight
genes—
MX1
,
B2M
IFIT1
TYMP
STAT1
IFI44
ISG15
IFI27
—affected
negative
regulation
biological
processes,
hepatitis
C
Epstein–Barr
viral
infection,
toll‐like
receptor
signaling
pathway,
mediate
after
infection.
In
particular,
played
a
central
role
process
regulating
biopathological
changes
during
SIVE.
Conclusion
These
findings
provide
new
theoretical
basis
for
treatment
encephalopathy
HIV
targeting
.
Language: Английский