bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Ноя. 4, 2023
The
human
papillomavirus
(HPV)
oncoprotein
E7
is
a
relatively
short-lived
protein
required
for
HPV-driven
cancer
development
and
maintenance.
degraded
through
ubiquitination
mediated
by
cullin
1
(CUL1)
the
ubiquitin-conjugating
enzyme
E2
L3
(UBE2L3).
However,
proteins
are
maintained
at
high
levels
in
most
HPV-positive
cells.
A
previous
proteomics
study
has
shown
that
UBE2L3
CUL1
increased
knockdown
of
E3
ubiquitin
ligase
membrane-associated
ring-CH-type
finger
8
(MARCHF8).
We
have
recently
demonstrated
HPV
upregulates
MARCHF8
expression
keratinocytes
head
neck
(HPV+
HNC)
Here,
we
report
stabilizes
degrading
components
SKP1-CUL1-F-box
(SCF)
complex
HPV+
HNC
found
Journal of Medical Virology,
Год журнала:
2024,
Номер
96(2)
Опубликована: Фев. 1, 2024
Abstract
Membrane‐associated
RING‐CH
(MARCH)
family
proteins
were
recently
reported
to
inhibit
viral
replication
through
multiple
modes.
Previous
work
showed
that
human
MARCH8
blocked
Ebola
virus
(EBOV)
glycoprotein
(GP)
maturation.
Our
study
here
demonstrates
MARCH1
and
MARCH2
share
a
similar
pattern
in
restricting
EBOV
GP‐pseudotyped
infection.
Human
retain
GP
at
the
trans
‐Golgi
network,
reduce
its
cell
surface
display,
impair
virions
infectivity.
Furthermore,
we
uncover
host
proprotein
convertase
furin
could
interact
with
MARCH1/2
intracellularly.
Importantly,
P
domain
is
verified
be
recognized
by
MARCH1/2/8,
which
critical
for
their
blocking
activities.
Besides,
bovine
murine
also
proteolytic
processing.
Altogether,
our
findings
confirm
of
different
mammalian
origins
relatively
conserved
feature
cleavage,
provide
clues
subsequent
MARCHs
antiviral
studies
may
facilitate
development
novel
strategies
antagonize
enveloped
Journal of Virology,
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 16, 2024
ABSTRACT
The
human
papillomavirus
(HPV)
oncoprotein
E7
is
a
relatively
short-lived
protein
required
for
HPV-driven
cancer
development
and
maintenance.
degraded
through
ubiquitination
mediated
by
cullin
1
(CUL1)
the
ubiquitin-conjugating
enzyme
E2
L3
(UBE2L3).
However,
proteins
are
maintained
at
high
levels
in
most
HPV-positive
cells.
A
previous
proteomics
study
has
shown
that
UBE2L3
CUL1
increased
knockdown
of
E3
ubiquitin
ligase
membrane-associated
ring-CH-type
finger
8
(MARCHF8).
We
have
recently
demonstrated
HPV16
upregulates
MARCHF8
expression
keratinocytes
head
neck
(HPV+
HNC)
Here,
we
report
stabilizes
degrading
components
S-phase
kinase-associated
1-CUL1-F-box
complex
HPV+
HNC
found
cells
drastically
decreases
level
while
increasing
levels.
further
revealed
binds
to
ubiquitinates
enhances
protein.
Conversely,
overexpression
suppresses
tumor
growth
vivo
.
Our
findings
suggest
HPV-induced
prevents
degradation
ubiquitinating
proteins.
IMPORTANCE
Since
essential
virus
replication;
HPV
maintain
HPV-infected
can
be
efficiently
ubiquitinated
proteasomes
host
cell.
Mechanistically,
(UBE2L3)
play
an
role
degradation.
show
membrane
(MARCHF8)
induced
E6
blocking
proteasomes.
knockout
restores
expression,
decreasing
inhibiting
proliferation
Additionally,
or
growth.
results
maintains
cell
inducing
MARCHF8,
which
may
critical
tumorigenesis.
Frontiers in Cellular and Infection Microbiology,
Год журнала:
2025,
Номер
14
Опубликована: Янв. 15, 2025
We
conducted
this
Research
Topic
to
explore
the
interaction
between
pathogens
and
host
cells,
revealing
how
achieve
cellular
infection
by
precisely
interacting
with
cell
proteins.
This
further
elucidates
cells
play
a
crucial
role
in
immune
defense,
blocking
pathogen
invasion
hindering
its
replication
expansion
within
cells.
Pathogen
is
one
of
most
serious
factors
threatening
development
livestock
industry
[1,2]
.
In-depth
exploration
molecular
mechanisms
underlying
pathogen-host
interactions
will
provide
solid
foundation
for
control
offer
critical
theoretical
support
antiviral
drugs,
vaccines,
therapeutic
antibodies
[3][4][5]
Through
more
refined
research
into
intracellular
co-evolution
mechanisms,
we
be
able
design
effective
diagnostic
methods
preventive
measures.
In
field
animal
disease
diagnosis,
numerous
new
technologies
have
been
applied
clinical
diagnostics
recent
years,
but
issues
such
as
low
sensitivity,
poor
accuracy,
slow
detection
speed
remain.
There
continuing
need
technologies,
including
both
pathogen-based
antibody-based
techniques,
which
can
faster,
accurate,
convenient
diagnosis
outbreaks.
Currently,
vaccine
prevention
remains
primary
means
controlling
diseases
[5]
Although
vaccines
various
developed,
many
still
suffer
from
safety
efficacy,
making
novel
strategies
significant
challenge
researchers
[6]
special
Topic,
published
Frontiers
Cellular
Infection
Microbiology,
represents
an
important
step
forward
understanding
themes
outlined
above.
Our
includes
20
key
studies
focuses
on
three
major
areas:
interactions,
diseases,
diseases.The
plays
central
infection,
evasion,
pathogenicity
[7]
Xu
et
al.
demonstrated
that
Pasteurella
multocida
(P.
multocida)
interacts
TLR2
receptor
macrophages,
activating
NF-κB
ERK1/2
signaling
pathways
promote
secretion
proinflammatory
cytokines,
facilitating
growth
spread.
The
study
confirmed
recombinant
protein
PMCNA_RS00975
P.
activates
through
TLR2,
contributing
virulence
multocida.
Jin
tuberculosis
(TB),
caused
Mycobacterium
(Mtb),
fatal
infectious
disease,
progression
involves
complex
system
Mtb.
IL-26,
member
IL-10
family,
has
antimicrobial
pro-inflammatory
functions.
They
found
IL-26
mRNA
levels
were
significantly
elevated
peripheral
blood
mononuclear
active
TB
patients,
while
plasma
lower.
stimulation
THP-1
promoted
polarization
M1
ROS
production,
killing
clarified
provided
basis
strategies.
These
findings
insights
responses
identify
potential
targets
intervention.This
also
establishment
detection.
With
increasing
diversity
prevalence
pathogens,
traditional
face
challenges
sensitivity
specificity.
Real-time
quantitative
PCR
TaqMan
PCR,
become
essential
tools
monitoring
pigs
poultry
due
their
high
specificity,
speed.
Wang
developed
quadruple
real-time
method
simultaneously
detect
gastrointestinal
(e.g.,
Salmonella,
Escherichia
coli,
Lawsonia
intracellularis,
Brachyspira
hyodysenteriae),
improving
efficiency,
avoiding
crossreactions,
meeting
epidemiological
needs.
Quan
four
similar
pigs,
helping
avoid
misdiagnosis
or
missed
symptoms.
Furthermore,
genotyping
Streptococcus
suis
Duck
circovirus,
rapid
accurate
facilitate
epidemic
control.
issue
reports
advances
antibody
diseases.
continuously
innovated,
enzyme-linked
immunosorbent
assay
(ELISA)
widely
used
monitor
status
pig
populations
regional
outbreak
SADS-CoV
China
economic
losses
poses
threat
industry.
Despite
surveys,
there
lack
long-term
data
extensive
serological
studies.
indirect
ELISA
based
S1
evaluate
978
serum
samples
29
provinces
2022
2023.
results
showed
overall
seroprevalence
59.97%,
provincial
ranging
16.7%
77.12%,
monthly
42.61%
68.45%.
Higher
was
observed
Northeast,
North
China,
Central
regions,
highest
spring
lowest
autumn.
evaluating
epidemiology
SADS-CoV,
formulating
measures,
developing
vaccines.Finally,
highlights
importance
subunit
monoclonal
offers
Mycoplasma
synoviae
(MS)
avian
causes
synovitis
respiratory
leading
substantial
losses.
Vaccination
preventing
MS
infections,
commercial
are
challenging
develop.
isolated
six
strains
different
performed
whole-genome
sequencing,
identified
22
common
genes
antigenic
targets.
epitope
prediction,
they
selected
10
candidate
proteins
eventually
multivalent
composed
MSPB,
Ppht,
Cfba,
EF-G,
protection
rate
90-100%,
providing
approach
development.
Du
achieved
soluble
expression
P32
Goatpox
virus
(GTPV)
specific
antibodies.
By
optimizing
gene
sequence
synthesizing
P32Δ
gene,
expressed
purified
rP32Δ
prokaryotic
system.
Using
immunize
mice,
established
hybridoma
lines
secreting
against
rP32Δ,
namely
2F3,
3E8,
4H5.
exhibited
good
3E8
specifically
recognizing
GTPV
provides
foundational
material
establishing
methods.As
continue
grow,
pathogenhost
evasion
areas
focus.
hope
reveal
multi-dimensional
roles
responses,
precise
intervention
detection,
improve
multiplex
enhance
application,
especially
efficient
during
research,
attention
should
given
personalized
precision
treatments,
safer
stronger
guarantees
health
food
safety.
covers
latest
methods,
development,
technical
It
contributes
transmission,
reduces
losses,
promotes
Veterinary Research,
Год журнала:
2025,
Номер
56(1)
Опубликована: Апрель 30, 2025
The
host
cell
membrane-associated
RING-CH8
protein
(MARCH8)
functions
as
an
antiviral
factor
by
targeting
viral
envelope
glycoproteins.
Foot-and-mouth
disease
virus
(FMDV)
is
a
non-enveloped,
positive-sense,
single-stranded
RNA
virus.
potential
impact
of
MARCH8
on
FMDV
replication
remains
uncertain.
Here,
we
found
that
the
overexpression
significantly
inhibited
in
dose-dependent
manner.
Conversely,
knockdown
facilitated
replication.
Specifically,
interacted
with
VP1,
VP2,
and
VP3,
mediating
their
degradation
proteasome-dependent
catalyzed
K33-linked
polyubiquitination
VP3.
Moreover,
Lys210
residue
Lys63
Lys118
VP3
were
identified
critical
target
sites
for
MARCH8-mediated
degradation.
Overall,
conclude
intrinsic
against
FMDV.
Cells,
Год журнала:
2024,
Номер
13(8), С. 698 - 698
Опубликована: Апрель 17, 2024
The
cellular
transmembrane
protein
MARCH8
impedes
the
incorporation
of
various
viral
envelope
glycoproteins,
such
as
HIV-1
glycoprotein
(Env)
and
vesicular
stomatitis
virus
G-glycoprotein
(VSV-G),
into
virions
by
downregulating
them
from
surface
virus-producing
cells.
This
downregulation
significantly
reduces
efficiency
infection.
In
this
study,
we
aimed
to
further
characterize
host
investigating
its
species
specificity
domains
responsible
for
antiviral
activity,
well
ability
inhibit
cell-to-cell
We
found
that
function
is
conserved
in
rhesus
macaque,
mouse,
bovine
versions.
RING-CH
these
versions
are
functionally
important
inhibiting
Env
VSV-G-pseudovirus
infection,
whereas
tyrosine
motifs
crucial
former
only,
consistent
with
findings
human
MARCH8.
Through
analysis
chimeric
proteins
between
non-antiviral
MARCH3,
determined
both
N-terminal
C-terminal
cytoplasmic
tails,
presumably
domain,
critical
activity.
Notably,
unable
block
likely
due
insufficient
Env.
These
offer
insights
understanding
biology
protein.
Journal of Virology,
Год журнала:
2024,
Номер
98(7)
Опубликована: Июнь 6, 2024
ABSTRACT
Nucleoprotein
(N)
is
well
known
for
its
function
in
the
encapsidation
of
genomic
RNAs
negative-strand
RNA
viruses,
which
leads
to
formation
ribonucleoproteins
that
serve
as
templates
viral
transcription
and
replication.
However,
N
protein
other
aspects
during
infection
far
from
clear.
In
this
study,
snakehead
vesiculovirus
(SHVV),
a
kind
fish
rhabdovirus,
was
proved
be
ubiquitinated
mainly
via
K63-linked
ubiquitination.
We
identified
nine
host
E3
ubiquitin
ligases
interacted
with
SHVV
N,
among
seven
facilitated
ubiquitination
protein.
Further
investigation
revealed
only
two
ligases,
Siah
ligase
2
(Siah2)
leucine-rich
repeat
sterile
alpha
motif
containing
1
(LRSAM1),
mediated
upregulated
expression
Siah2
LRSAM1,
maintained
stability
N.
Besides,
overexpression
or
LRSAM1
promoted
replication,
while
knockdown
inhibited
Deletion
domain
did
not
affect
their
interactions
but
reduced
summary,
mediate
facilitate
provides
novel
insights
into
role
proteins
viruses.
IMPORTANCE
Ubiquitination
plays
an
important
nucleoprotein
viruses
has
rarely
been
investigated.
This
study
aimed
at
investigating
rhabdovirus
(snakehead
vesiculovirus),
identifying
related
determining
found
ubiquitination,
by
(Siah
2)
(leucine-rich
1).
The
data
suggested
were
hijacked
ubiquitinate
exhibited
anti-SHVV
targets
drug
design.
