Experimental & Molecular Medicine,
Journal Year:
2024,
Volume and Issue:
56(11), P. 2475 - 2490
Published: Nov. 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,
Journal Year:
2024,
Volume and Issue:
633(8030), P. 710 - 717
Published: Aug. 26, 2024
Abstract
The
rapid
evolution
of
viruses
generates
proteins
that
are
essential
for
infectivity
and
replication
but
with
unknown
functions,
due
to
extreme
sequence
divergence
1
.
Here,
using
a
database
67,715
newly
predicted
protein
structures
from
4,463
eukaryotic
viral
species,
we
found
62%
structurally
distinct
lack
homologues
in
the
AlphaFold
2,3
Among
remaining
38%
proteins,
many
have
non-viral
structural
analogues
revealed
surprising
similarities
between
human
pathogens
their
hosts.
Structural
comparisons
suggested
putative
functions
up
25%
unannotated
including
those
roles
evasion
innate
immunity.
In
particular,
RNA
ligase
T-like
phosphodiesterases
were
resemble
phage-encoded
hydrolyse
host
immune-activating
cyclic
dinucleotides
3′,3′-
2′,3′-cyclic
GMP-AMP
(cGAMP).
Experimental
analysis
showed
T
encoded
by
avian
poxviruses
similarly
cGAMP,
showing
T-mediated
targeting
cGAMP
is
an
evolutionarily
conserved
mechanism
immune
present
both
bacteriophage
viruses.
Together,
analyses
presented
here
afford
new
opportunities
identify
mechanisms
virus–host
interactions
common
across
virome.
Nucleic Acids Research,
Journal Year:
2024,
Volume and Issue:
53(D1), P. D340 - D347
Published: Nov. 22, 2024
Abstract
The
AlphaFold
Protein
Structure
Database
(AFDB)
is
the
largest
repository
of
accurately
predicted
structures
with
taxonomic
labels.
Despite
providing
predictions
for
over
214
million
UniProt
entries,
AFDB
does
not
cover
viral
sequences,
severely
limiting
their
study.
To
address
this,
we
created
Big
Fantastic
Virus
(BFVD),
a
351
242
protein
by
applying
ColabFold
to
sequence
representatives
UniRef30
clusters.
By
utilizing
homology
searches
across
two
petabases
assembled
sequencing
data,
improved
36%
these
structure
beyond
ColabFold’s
initial
results.
BFVD
holds
unique
repertoire
as
62%
its
entries
show
no
or
low
structural
similarity
existing
repositories.
We
demonstrate
how
substantial
fraction
bacteriophage
proteins,
which
remained
unannotated
based
on
can
be
matched
similar
from
BFVD.
In
that,
par
AFDB,
while
holding
nearly
three
orders
magnitude
fewer
structures.
an
important
virus-specific
expansion
repositories,
offering
new
opportunities
advance
research.
freely
downloaded
at
bfvd.steineggerlab.workers.dev
and
queried
using
Foldseek
labels
bfvd.foldseek.com.
Proceedings of the National Academy of Sciences,
Journal Year:
2024,
Volume and Issue:
121(8)
Published: Feb. 12, 2024
Monkeypox
virus
(MPXV)
infections
in
humans
cause
neurological
disorders
while
studies
of
MPXV-infected
animals
indicate
that
the
penetrates
brain.
Pyroptosis
is
an
inflammatory
type
regulated
cell
death,
resulting
from
plasma
membrane
rupture
(PMR)
due
to
oligomerization
cleaved
gasdermins
pore
formation.
Herein,
we
investigated
human
neural
tropism
MPXV
compared
another
orthopoxvirus,
vaccinia
(VACV),
as
well
its
effects
on
immune
responses
and
death.
Astrocytes
were
most
permissive
(and
VACV)
infections,
followed
by
microglia
oligodendrocytes,
with
minimal
infection
neurons
based
plaque
assays.
Aberrant
morphological
changes
evident
astrocytes
accompanied
viral
protein
(I3)
immunolabelling
detection
over
125
MPXV-encoded
proteins
lysates
mass
spectrometry.
MPXV-
VACV-infected
showed
increased
expression
gene
transcripts
(
IL12,
IRF3,
IL1B,
TNFA,
CASP1
,
GSDMB
).
However,
specifically
induced
proteolytic
cleavage
gasdermin
B
(GSDMB)
(50
kDa),
appearance
N-terminal-GSDMB
(30
kDa)
C-terminal-
(18
fragments.
was
associated
release
lactate
dehydrogenase
cellular
nucleic
acid
staining,
indicative
PMR.
Pre-treatment
dimethyl
fumarate
reduced
PMR
astrocytes.
Human
support
productive
infection,
induction
accompanying
GSDMB-mediated
pyroptosis.
These
findings
clarify
recently
recognized
neuropathogenic
also
offering
potential
therapeutic
options.
PLoS Biology,
Journal Year:
2024,
Volume and Issue:
22(7), P. e3002717 - e3002717
Published: July 15, 2024
Immune
defence
mechanisms
exist
across
the
tree
of
life
in
such
diversity
that
prokaryotic
antiviral
responses
have
historically
been
considered
unrelated
to
eukaryotic
immunity.
Mechanisms
divergent
eukaryotes
were
similarly
believed
be
largely
clade
specific.
However,
recent
data
indicate
a
subset
modules
(domains
and
proteins)
from
prokaryote
systems
are
conserved
populate
many
stages
innate
immune
pathways.
In
this
Essay,
we
propose
notion
ancestral
immunity,
which
corresponds
set
between
prokaryotes
eukaryotes.
After
offering
typology
speculate
on
selective
pressures
could
led
differential
conservation
specific
domains
life.
The
exploration
immunity
is
its
infancy
appears
full
promises
illuminate
evolution,
also
identify
decipher
economic,
ecological,
therapeutic
importance.
Journal of Innate Immunity,
Journal Year:
2024,
Volume and Issue:
unknown
Published: Aug. 13, 2024
The
re-emergence
of
the
Mpox
(formerly
monkeypox)
in
2022
non-endemic
countries
has
raised
many
concerns
for
global
health
due
to
its
high
transmissibility
and
mortality
rate.
A
major
challenge
fighting
is
ability
evade
host's
innate
immune
system,
which
first
line
defense
against
viral
infections.
encodes
various
proteins
that
interfere
with
key
antiviral
pathways
mechanisms,
such
as
nuclear
factor
kappa
B
(NF-κB)
signaling,
cytokine
production,
complement
inflammasome
activation,
chemokine
binding.
These
modulate
expression
function
mediators,
interferons,
interleukins,
toll-like
receptors,
impair
recruitment
activation
cells,
natural
killer
cells.
By
suppressing
or
altering
these
responses,
enhances
replication
infection
host
tissues
organs,
leading
systemic
inflammation,
tissue
damage,
organ
failure.
This
study
reveals
new
insights
into
molecular
cellular
interactions
between
host’s
immunity
identifies
potential
targets
strategies
interventions.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2024,
Volume and Issue:
unknown
Published: Sept. 9, 2024
The
AlphaFold
Protein
Structure
Database
(AFDB)
is
the
largest
repository
of
accurately
predicted
structures
with
taxonomic
labels.
Despite
providing
predictions
for
over
214
million
UniProt
entries,
AFDB
does
not
cover
viral
sequences,
severely
limiting
their
study.
To
bridge
this
gap,
we
created
Big
Fantastic
Virus
(BFVD),
a
351,242
protein
by
applying
ColabFold
to
sequence
representatives
UniRef30
clusters.
BFVD
holds
unique
repertoire
as
63%
its
entries
show
no
or
low
structural
similarity
existing
repositories.
We
demonstrate
how
substantially
enhances
fraction
annotated
bacteriophage
proteins
compared
sequence-based
annotation
using
Bakta.
In
that,
on
par
AFDB,
while
holding
nearly
three
orders
magnitude
fewer
structures.
an
important
virus-specific
expansion
structure
repositories,
offering
new
opportunities
advance
research.
freely
available
at
https://bfvd.steineggerlab.workers.dev/
PubMed,
Journal Year:
2025,
Volume and Issue:
15(1), P. 339 - 347
Published: Jan. 1, 2025
Urethral
catheterization
in
the
critical
care
unit
often
compromises
urinary
tract's
defense
mechanisms
of
canine
patients
and
potentially
leads
to
hospital-acquired
systemic
infection.
Clinical
signs
catheter-associated
tract
infections
(CAUTIs)
are
frequently
absent
dogs.
This
study
aimed
evaluate
correlation
between
urinalysis
results
CAUTIs
dogs
assess
impact
prior
antibiotic
treatment
for
underlying
diseases
antibiotic-resistant
bacteria.
Twenty-eight
underwent
urethral
Kasetsart
University
Veterinary
Teaching
Hospital.
Bacterial
cultures
drug
sensitivity
tests
were
performed
immediately
after
catheter
placement
(day
0),
3,
7
before
removal.
A
positive
urine
culture
was
defined
as
≥104
CFU/ml.
Urinalysis
parameters
included
pH,
specific
gravity,
proteinuria,
bacteriuria,
pyuria,
hematuria.
Only
with
culture-negative
on
day
0
included.
Data
analyzed
using
GraphPad
Prism
version
10.0.2.
Kaplan-Meier
survival
analysis
used
probability
being
free
from
over
time.
No
significant
association
observed
parameters,
duration,
breed,
sex,
neutering
status,
or
age.
Dogs
pretreated
antibiotics
exhibited
CAUTI-free
periods
longer
than
previously
reported.
The
showed
that
probabilities
92.8%
at
3
days,
declining
60.7%
by
days
53.6%
10
days.
Alarmingly,
80%
isolates
(12/15)
multidrug-resistant
organisms
(MDRO)
resistant
≥3
antimicrobials.
high
incidence
detected
13
28
cases
(46.4%).
stayed
hospital
without
CAUTIs.
routine
is
unreliable
predicting
rate
MDRO
among
underscores
urgent
need
judicious
use
enhanced
diagnostic
methods
settings.
proposes
serial
bacterial
combined
modified
sediment
examinations
can
better
manage
CAUTI
detection
reduce
growth
MDROs
veterinary
practice.
mBio,
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 20, 2025
ABSTRACT
Poxviruses
comprise
pathogens
that
are
highly
pathogenic
to
humans
and
animals,
causing
diseases
such
as
smallpox
mpox
(formerly
monkeypox).
The
family
also
contains
members
developed
vaccine
vectors
oncolytic
agents
fight
other
diseases.
Vaccinia
virus
is
the
prototype
poxvirus
used
eradicate
smallpox.
Poxvirus
genes
follow
a
cascade
temporal
expression
pattern,
categorized
into
early,
intermediate,
late
stages
using
distinct
transcription
factors.
This
review
comprehensively
summarized
classification
of
over
200
vaccinia
genes.
relationships
between
classes
functions,
well
different
branches
immune
responses,
were
discussed.
Based
on
orthologs,
we
classified
all
genes,
including
few
not
previously
annotated
with
orthologs
in
viruses.
Additionally,
reviewed
functions
based
up-to-date
published
papers.
provides
readily
usable
resource
for
researchers
working
biology,
medical
countermeasures,
utility
development.