Type I interferon autoantibody footprints reveal neutralizing mechanisms and allow inhibitory decoy design
The Journal of Experimental Medicine,
Год журнала:
2025,
Номер
222(6)
Опубликована: Март 20, 2025
Autoantibodies
neutralizing
type
I
interferons
(IFN-Is;
IFNα
or
IFNω)
exacerbate
severe
viral
disease,
but
specific
treatments
are
unavailable.
With
footprint
profiling,
we
delineate
two
dominant
IFN-I
faces
commonly
recognized
by
autoantibody–containing
plasmas
from
aged
individuals
with
HIV-1
and
COVID-19.
These
overlap
regions
independently
essential
for
engaging
the
IFNAR1/IFNAR2
heterodimer,
efficiently
block
interaction
of
both
receptor
subunits
in
vitro.
In
contrast,
non-neutralizing
limit
only
one
subunit
display
relatively
low
IFN-I–binding
avidities,
thus
likely
hindering
function.
Iterative
engineering
signaling-inert
mutant
IFN-Is
(simIFN-Is)
retaining
autoantibody
targets
created
potent
decoys
that
prevent
neutralization
autoantibody-containing
restore
IFN-I–mediated
antiviral
activity.
Additionally,
microparticle-coupled
simIFN-Is
were
effective
at
depleting
autoantibodies
plasmas,
leaving
antibodies
unaffected.
Our
study
reveals
mechanisms
action
demonstrates
a
proof-of-concept
strategy
to
alleviate
pathogenic
effects.
Язык: Английский
Powassan and other emerging neuroinvasive arboviruses in North America
Current Opinion in Infectious Diseases,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 30, 2025
Purpose
of
review
Arthropod-borne
viruses
(arboviruses)
represent
a
group
pathogens
with
increasing
global
relevance,
some
which
cause
neuroinvasive
disease.
Transmitted
by
arthropod
vectors
and
maintained
variety
primary
amplifying
hosts,
epidemics
are
dependent
on
numerous
environmental
anthropogenic
factors.
This
serves
to
highlight
several
important
arboviruses
relevant
North
America
discuss
the
neurologic
presentations,
diagnosis,
outcomes,
future
trends.
Recent
findings
shifts
in
epidemiology
ecology
include
divergence
such
as
dengue
chikungunya
from
dependence
enzootic
cycles,
geographical
expansion
Oropouche
virus,
incidence
established
American
Powassan
virus.
Accurate
identification
factors
contributing
arboviral
outbreaks
is
critical
improve
preventive
public
health
measures.
Similarly,
further
elucidating
pathogen
host
that
determine
neuroinvasiveness,
neurotropism,
neurovirulence
will
be
key
development
successful
vaccines
targeted
therapeutics.
Summary
Arboviruses
an
human
Familiarity
diagnostic
workup,
treatment
strategies,
expected
course
for
clinicians
caring
these
patients.
Язык: Английский
Human type I interferons protect Vero E6 and ARPE-19 cells against West Nile virus and are neutralized by pathogenic autoantibodies
Scientific Reports,
Год журнала:
2025,
Номер
15(1)
Опубликована: Апрель 2, 2025
Auto-antibodies
(auto-Abs)
that
neutralize
type
I
interferons
(IFNs)
have
been
implicated
in
severe
viral
infections,
including
~
40%
of
cases
West
Nile
virus
(WNV)
neuroinvasive
disease
(WNND).
Developing
robust
vitro
models
to
evaluate
the
protective
effects
IFNs
against
infection,
as
well
disruptive
auto-Abs,
is
essential
for
understanding
pathogenesis
and
identifying
patients
at
risk.
In
this
study,
we
used
Vero
E6
ARPE-19
cell
lines
investigate
ability
(IFN-α,
IFN-β,
IFN-ω),
II
(IFN-γ),
III
(IFN-λ1)
restrict
WNV
infection.
Our
results
demonstrate
IFN-α,
IFN-ω
effectively
protect
cells
from
with
IFN-β
exhibiting
strongest
antiviral
effect.
contrast,
required
higher
concentrations
achieve
comparable
protection.
Neither
IFN-γ
nor
IFN-λ1
conferred
protection
either
line.
We
further
screened
serum
samples
WNV-infected
auto-Abs
neutralizing
IFNs.
findings
confirm
ARPE-19-based
assay
consistent
other
established
methods
detecting
This
simple
reliable
offers
a
valuable
tool
assessing
activity
both
research
clinical
settings.
Future
studies
should
aim
validate
utility
ARPE-19-WNV
infection
model
on
larger
scale.
Язык: Английский
Deciphering the autoreactome: Massively parallelized methods for autoantibody detection in humans
Journal of Immunological Methods,
Год журнала:
2025,
Номер
unknown, С. 113876 - 113876
Опубликована: Май 1, 2025
Язык: Английский
Inborn Errors of Nucleic Acid Sensing and Type I Interferon Signaling Determine Viral Susceptibility in Humans
European Journal of Immunology,
Год журнала:
2025,
Номер
55(5)
Опубликована: Май 1, 2025
The
innate
immune
system
relies
on
nucleic
acid
(NA)
sensors
to
detect
viral
infections
and
trigger
type
I
interferon
(IFN-I)
responses,
which
are
crucial
for
antiviral
defense.
NA
pattern
recognition
receptors
RNA
or
DNA
within
various
cellular
compartments,
initiating
signaling
pathways.
However,
inherited
deficiencies
in
these
sensing
mechanisms
can
result
increased
susceptibility
severe
infections.
This
review
explores
key
genetic
mutations
affecting
IFN-I
pathways
that
predispose
individuals
life-threatening
diseases,
including
herpesviruses,
respiratory
viruses,
enteroviruses,
arboviruses,
vaccine-strain
disseminated
diseases.
identification
of
monogenic
defects
afflicted
by
infections,
along
with
the
observed
incomplete
penetrance
mutations,
highlight
intricate
interplay
host's
intrinsic,
innate,
adaptive
response
invading
pathogens.
These
insights
into
molecular
basis
immunity
not
only
underscore
clinical
challenges
associated
but
also
offers
opportunity
personalized
treatment
strategies,
screening,
tailored
vaccination
protocols,
targeted
therapies.
Язык: Английский