Experimental & Molecular Medicine,
Год журнала:
2024,
Номер
56(11), С. 2475 - 2490
Опубликована: Ноя. 1, 2024
Poxviruses
are
implicated
in
a
variety
of
infectious
diseases;
however,
little
is
known
about
the
molecular
mechanisms
that
underlie
immune
response
during
poxvirus
infection.
We
investigated
function
and
monkeypox
virus
envelope
protein
(A30L)
its
core
peptide
(IAMP29)
activation
innate
responses.
The
A30L
peptide,
IAMP29
(a
29-amino-acid
inflammasome-activating
encompassing
His40
to
Asp69
A30L),
strongly
activated
nucleotide-binding
oligomerization
domain,
leucine
rich
repeat
pyrin
domain-containing
3
(NLRP3)
inflammasome
by
inducing
production
mitochondrial
reactive
oxygen
species
human
monocytes.
Specifically,
triggered
metabolic
reprogramming
toward
glycolysis
interacted
with
pyruvate
kinase
M
isoforms
(PKM1
PKM2),
thus
activating
NLRP3
interleukin
(IL)-1β
monocytes
murine
macrophages.
In
primary
monocyte-derived
macrophages,
IAMP29-induced
promoted
an
antimicrobial
rapidly
growing
non-tuberculous
mycobacteria.
Furthermore,
exhibited
cytotoxic
activity
against
leukemia
cells,
which
was
mediated
pyroptosis
apoptosis.
These
findings
provide
insights
into
immunological
suggest
therapeutic
potential.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Дек. 8, 2023
Abstract
Modified
vaccinia
Ankara
(MVA)
virus
does
not
replicate
in
human
cells
and
is
the
vaccine
deployed
to
curb
current
outbreak
of
mpox.
Here,
we
conduct
a
multiplexed
proteomic
analysis
quantify
>9000
cellular
~80%
viral
proteins
throughout
MVA
infection
fibroblasts
macrophages.
>690
are
down-regulated
>2-fold
by
MVA,
revealing
substantial
remodelling
host
proteome.
>25%
these
targets
shared
with
replication-competent
vaccinia.
Viral
intermediate/late
gene
expression
necessary
for
antagonism
innate
immunity,
suppression
interferon
effectors
such
as
ISG20
potentiates
expression.
Proteomic
changes
specific
macrophages
indicate
modulation
inflammatory
response,
including
inflammasome
activation.
Our
approach
thus
provides
global
view
impact
on
proteome
identifies
mechanisms
that
may
underpin
its
abortive
infection.
These
discoveries
will
prove
vital
design
future
generations
vaccines.
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Март 20, 2024
The
gasdermin
protein
family
and
its
homologs
in
microorganisms
have
gained
significant
attention
due
to
their
roles
programmed
cell
death,
immune
defense,
microbial
infection.
This
review
summarizes
the
current
research
status
of
proteins,
structural
features,
functional
fungi,
bacteria,
viruses.
presents
evolutionary
parallels
between
mammalian
defense
systems,
highlighting
conserved
role
proteins
regulating
death
processes
immunity.
Additionally,
characteristics
are
summarized,
shedding
light
on
potential
as
targets
for
therapeutic
interventions.
Future
directions
this
field
also
discussed
provide
a
roadmap
further
investigation.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 6, 2024
Abstract
The
sensing
of
viral
nucleic
acid
by
pattern
recognition
receptors
(PRRs)
is
essential
for
initiation
a
type-I
interferon
response
against
infection.
Intracellular
DNA
PRRs
are
responsible
initiating
innate
immune
responses
to
poxviruses
and
other
double-stranded
viruses.
Poxviruses,
in
turn,
encode
an
armoury
immunomodulators
that
inhibit
this
host
defence
mechanism.
DNA-dependent
protein
kinase
(DNA-PK)
component
the
cGAS/STING-dependent
machinery
leads
during
poxvirus
Poxviruses
counter
mechanism
using
C4/C10
family
proteins
target
DNA-PK,
interfering
with
its
ability
bind
DNA.
Although
DNA-PK
complex,
known
also
role
double
strand
break
repair,
conserved
across
multiple
taxa,
function
immunity
outside
mammals
unexplored.
Here
we
analysed
contribution
chickens,
species
evolutionarily
distant
from
mammals,
but
infected
poxviruses.
We
found
functions
as
sensor
process
countered
members
fowlpox
virus.
This
host/pathogen
interaction
broader
range
than
mechanisms
antagonism
sensing,
which
may
reflect
difficulty
evolving
escape
interfere
maintenance
genomic
stability.
Experimental & Molecular Medicine,
Год журнала:
2024,
Номер
56(11), С. 2475 - 2490
Опубликована: Ноя. 1, 2024
Poxviruses
are
implicated
in
a
variety
of
infectious
diseases;
however,
little
is
known
about
the
molecular
mechanisms
that
underlie
immune
response
during
poxvirus
infection.
We
investigated
function
and
monkeypox
virus
envelope
protein
(A30L)
its
core
peptide
(IAMP29)
activation
innate
responses.
The
A30L
peptide,
IAMP29
(a
29-amino-acid
inflammasome-activating
encompassing
His40
to
Asp69
A30L),
strongly
activated
nucleotide-binding
oligomerization
domain,
leucine
rich
repeat
pyrin
domain-containing
3
(NLRP3)
inflammasome
by
inducing
production
mitochondrial
reactive
oxygen
species
human
monocytes.
Specifically,
triggered
metabolic
reprogramming
toward
glycolysis
interacted
with
pyruvate
kinase
M
isoforms
(PKM1
PKM2),
thus
activating
NLRP3
interleukin
(IL)-1β
monocytes
murine
macrophages.
In
primary
monocyte-derived
macrophages,
IAMP29-induced
promoted
an
antimicrobial
rapidly
growing
non-tuberculous
mycobacteria.
Furthermore,
exhibited
cytotoxic
activity
against
leukemia
cells,
which
was
mediated
pyroptosis
apoptosis.
These
findings
provide
insights
into
immunological
suggest
therapeutic
potential.
