Wiley Interdisciplinary Reviews - RNA,
Год журнала:
2024,
Номер
15(6)
Опубликована: Ноя. 1, 2024
ABSTRACT
Ribonuclease
L
is
an
endonuclease
that
activated
as
part
of
the
dsRNA‐driven
innate
immune
response.
Active
RNase
cleaves
pathogenic
RNAs
a
way
to
eliminate
infections.
However,
there
are
additional
and
unexpected
ways
causes
changes
in
host
promote
response
contribute
its
role
defense.
Central
these
unconventional
mechanisms
observation
also
degrades
mRNA
host.
In
turn,
fragments
generates
can
be
translated.
This
activation
ribosome
collision
sensor
leads
downstream
signaling
cell
death.
Additionally,
liberation
RNA
binding
proteins
after
decay
appears
affect
gene
expression.
this
review,
we
discuss
other
recent
advances
focus
on
novel
unusual
contributes
immunity.
ABSTRACT
The
coronavirus
disease
2019
(COVID-19)
pandemic
remains
an
international
health
problem
caused
by
the
recent
emergence
of
severe
acute
respiratory
syndrome
2
(SARS-CoV-2).
As
May
2024,
SARS-CoV-2
has
more
than
775
million
cases
and
over
7
deaths
globally.
Despite
current
vaccination
programs,
infections
are
still
rapidly
increasing,
mainly
due
to
appearance
spread
new
variants,
variations
in
immunization
rates,
limitations
vaccines
preventing
transmission.
This
underscores
need
for
pan-variant
antivirals
treatments.
interferon
(IFN)
system
is
a
critical
element
innate
immune
response
serves
as
frontline
defense
against
viruses.
It
induces
generalized
antiviral
state
transiently
upregulating
hundreds
IFN-stimulated
genes
(ISGs).
To
gain
deeper
comprehension
SARS-CoV-2,
its
connection
COVID-19
pathogenesis,
potential
therapeutic
implications,
this
review
provides
detailed
overview
fundamental
aspects
diverse
ISGs
identified
their
properties
SARS-CoV-2.
emphasizes
importance
these
proteins
controlling
viral
replication
spread.
Furthermore,
we
explore
methodological
approaches
identification
conduct
comparative
analysis
with
other
Deciphering
roles
interactions
pathogens
can
help
identify
novel
targets
therapies
enhance
our
preparedness
confront
future
threats.
Veterinary Sciences,
Год журнала:
2025,
Номер
12(3), С. 288 - 288
Опубликована: Март 19, 2025
West
Nile
virus
(WNV)
is
an
important
zoonotic
pathogen
belonging
to
the
Flaviviridae
family,
which
endemic
in
some
areas
and
emerging
others.
WNV
transmitted
by
blood-sucking
mosquitoes
of
genus
Culicoides,
Aedes,
Anopheles,
infection
can
cause
different
clinical
symptoms.
The
most
common
benign
illness
humans
fever
(WNF),
but
a
lethal
neurological
disease
(WNND),
related
neuro-invasiveness
lineage
2,
represents
highest
health
risk
infection.
neuro-clinical
form
recognized
mammals
(land
cetaceans),
particularly
(elderly
or
immunosuppressed)
horses,
avian
species,
wildlife
animals
ranging
free
zoological
setting.
This
review
highlights
relevant
data
regarding
epidemiology,
virology,
pathogenesis
immunity,
signs
differential
diagnosis,
pathology
imaging,
histopathology
gross
pathology,
economic
impact,
influence
climate
change,
surveillance
WNV.
Climate
change
has
favored
wide
spread
many
globe
consequent
One-Health
Eco-Health
emergencies,
influencing
human
beings,
animals,
ecosystems.
Abstract
Chronic
inflammation
plays
an
obscure
role
in
cancer
initiation,
with
broad
references
implicating
immune
exhaustion
(IEX)
or
free
radical
mediated
cell
damage.
is,
however,
paradoxically
synonymous
the
term
“immune
tolerance”
which
other
cases
presents
itself
as
a
therapeutic
limitation
to
efficacy
of
tumor
therapies
particularly
those
involving
microbial
-associated
molecular
patterns
(MAMPs)
regimens.
As
“tolerance”
remains
this
day
“phenomenon”
there
is
pressing
need
fully
understand
every
biological
aspect
apparent
negative
feedback
response,
because
doing
so
will
serve
guide
development
targeted
therapies.
In
work,
we
employ
rudimentary
model,
can
be
adopted
it
possible
provoke
through
sustained
antigen
stimulation
immunocompetent
cells,
monitor,
define
and
characterize
phenotype
evolution
using
next
generation
whole
transcriptome
sequencing
+
validation
studies.
This
model
used
study
/create
vitro
“M2”
phenotype,
involved
aggressive
tumors
synergistic
rapid
expansion
myeloid-derived
suppressor
cells
(MDSCs),
dysfunctional
CD8+
T
cytotoxic
(CTL)/
natural
killer
(NK)
cells.
Briefly,
data
shows
dominates
at
7
11
days,
after
acute
being
associated
phase
specific
(time
dependent)
elevated
checkpoints;
e.g.
PDL1+/MSN,
HAVCR2/TIM-3+,
SPP1+,
C3ar1+,
CD73+,
IL1RN+,
LILRbs+,
glycoproteins,
integrins
etc.
Here
report
on
bidirectional
changes
aligning
escape,
much
centered
around
loss
host
defense
against
viral
infection
malignancy.
Negative
rampant
induction
degradative
proteases,
SOCS/JAK/STAT/IL-10,
CCL2/7
axis
tantamount
MHC1/2
recognition
systems,
Type
I
interferon
NOD
signaling,
antiviral/antibacterial
defense,
p62/SQSTM
also
disturbed
metabolic
signature.
The
work
demonstrates
that
colloquial
terms
“tolerance
IEX”
are
somewhat
flawed
terminology,
potent,
intentional
formidable
offense
eradicate
active
arm
defense.
Truncated
/Removed
due
word
count
show
aligns
six
distinct
chronological
differential
gene
(DEG)
expression
circumscribe
extensive
suppression
dominate
during
chronic
inflammation.
These
involve
following
time
dependent
patterns:
1)
transcripts
overexpressed,
checkpoint
receptors;
etc.;
2)
overexpressed
only
chronic;
e.g
cytokine
signaling
(SOC3/Jak/Stat),
cyto/chemokines
(IL-10,
CCL2,
CCL7),
proteases
(cathepsins
L,
D,
K,
Adam
8,
PIM2),
adhesives
(TSPAN3,
QSOX1,
PDPN,
ITGA5),
(PLK2,
ADGRE1,
CALM1,
PCNA,
etc.);
3)
downregulated
severe
collective
MHC1/II
presentation
capacity
(CD74,
H2-Q4,
H2-Q6,
etc.),
(IFN)
type
systems;
4)
only,
including
OXPHOS/metabolic
genes
(Aldo
A,
C,
Eno2,
Gpi1,
(Lyz1,
Lyz2,
Card19,
Ninj1),
autophagy-related
(p62/SQSTM1).
category
Tolerance
were:
5)
induced
sharply
acute,
no
longer
responsive
IFN
1
antiviral
response
(OAS,
BST2,
ISG15,
ISG20,
IRF7,
RSAD2/Viperin),
TLR2,
antibacterial
(SAA3,
SP140),
proinflammatory
cytokines
(CCL5,
TNF,
IL1a,
IL1b)
along
IL-1/TLR
axis.
Last,
6)
reverse
tolerance,
corresponded
restored
baseline
levels
maintain
mitotic
thymosin
homeostasis.
conclusion,
these
suggest
precipitates
feedback,
same
targets
sought
today
Oligoadenylate
synthetase
(OAS)
proteins
are
immune
sensors
for
double-stranded
RNA
and
critical
restricting
viruses.
OAS2
comprises
two
OAS
domains,
only
one
of
which
can
synthesize
2'-5'-oligoadenylates
RNase
L
activation.
Existing
structures
OAS1
provide
a
model
enzyme
activation,
but
they
do
not
explain
how
multiple
domains
discriminate
length.
Here,
we
discover
that
human
exists
in
an
auto-inhibited
state
as
zinc-mediated
dimer
present
mechanism
length
discrimination:
the
catalytically
deficient
domain
acts
molecular
ruler
prevents
autoreactivity
to
short
RNAs.
We
demonstrate
dimerization
myristoylation
localize
Golgi
membranes
this
is
required
activation
restriction
viruses
exploit
endomembrane
system
replication,
e.g.,
coronaviruses.
Finally,
our
results
highlight
non-redundant
role
emphasize
clinical
relevance
by
identifying
patient
with
loss-of-function
mutation
associated
autoimmune
disease.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июль 30, 2024
Abstract
The
rodent-borne
Andes
virus
(ANDV)
causes
a
severe
disease
in
humans.
We
developed
an
ANDV
mRNA
vaccine
based
on
the
M
segment
of
viral
genome,
either
with
regular
uridine
(U-mRNA)
or
N1-methylpseudouridine
(m1Ψ-mRNA).
Female
mice
immunized
by
m1Ψ-mRNA
slightly
greater
germinal
center
(GC)
responses
than
U-mRNA-immunized
mice.
Single
cell
RNA
and
BCR
sequencing
GC
B
cells
revealed
similar
levels
activation,
except
additional
cluster
exhibiting
interferon
response
animals
vaccinated
U-mRNA
but
not
m1Ψ-mRNA.
Similar
immunoglobulin
class-switching
somatic
hypermutations
were
observed
to
vaccines.
Syrian
hamsters
via
prime–boost
regimen
two
doses
each
vaccine.
titers
glycoprotein-binding
antibodies
for
construct
construct;
however,
ANDV-neutralizing
similar.
Vaccinated
challenged
lethal
dose
ANDV,
along
naïve
control
group.
All
lower
succumbed
infection
whereas
other
survived
without
evidence
replication.
data
demonstrate
development
protective
against
lack
substantial
effect
m1Ψ
modification
immunogenicity
protection
rodents.
