Pseudotyped Viruses: A Useful Platform for Pre-Clinical Studies Conducted in a BSL-2 Laboratory Setting
Biomolecules,
Journal Year:
2025,
Volume and Issue:
15(1), P. 135 - 135
Published: Jan. 15, 2025
The
study
of
pathogenic
viruses
has
always
posed
significant
biosafety
challenges.
In
particular,
the
highly
requires
methods
with
low
biological
risk
but
relatively
high
sensitivity
and
convenience
in
detection.
recent
years,
pseudoviruses,
which
consist
a
backbone
one
virus
envelope
proteins
another
virus,
have
become
most
widely
used
tools
for
exploring
mechanisms
binding
to
cells,
membrane
fusion
viral
entry,
as
well
screening
libraries
antiviral
substances,
evaluating
potential
neutralizing
monoclonal
antibodies,
developing
neutralization
tests,
therapeutic
platforms.
During
outbreak
severe
acute
respiratory
syndrome
coronavirus
2
(SARS-CoV-2),
pseudotyped
virus-based
assays
played
pivotal
role
advancing
our
understanding
virus-cell
interactions
its
disease
pathogenesis.
Such
facilitated
search
agents
accelerated
epidemiological
studies
on
post-infection
post-vaccination
humoral
immunity.
This
review
focuses
use
pseudoviruses
model
large-scale
applications
enveloped
viruses.
Language: Английский
NIEAs elicited by wild-type SARS-CoV-2 primary infection fail to enhance the infectivity of Omicron variants
Virology Journal,
Journal Year:
2025,
Volume and Issue:
22(1)
Published: Feb. 24, 2025
SARS-CoV-2
infection
widely
induces
antibody
response
targeting
diverse
viral
proteins,
including
typical
representative
N-terminal
domain
(NTD),
receptor-binding
(RBD),
and
S2
subunit
of
spike.
A
lot
NTD-,
RBD-,
S2-specific
monoclonal
antibodies
(mAbs)
have
been
isolated
from
COVID-19
convalescents,
some
which
displaying
potent
activities
to
inhibit
infection.
However,
a
small
portion
NTD-specific
mAbs
elicited
by
wild-type
(WT)
primary
could
facilitate
the
virus
entry
into
target
cells
in
vitro,
so
called
NTD-targeting
infection-enhancing
(NIEAs).
To
date,
has
evolved
massive
variants
carrying
various
NTD
mutations,
especially
recent
Omicron
BA.2.86
JN.1.
In
this
study,
we
investigated
whether
these
WT-NIEAs
still
enhance
infectivity
emerging
variants.
Nine
novel
with
germline
gene
usage
were
identified
3
individuals,
effectively
enlarging
available
panel
NIEAs.
Bivalent
binding
NIEAs
inter-spike
contributed
their
activities.
emerged
before
Omicron,
but
ineffective
JN.1,
was
because
changed
antigenicity
NTDs.
Overall,
data
clearly
demonstrated
cross-reactivity
pre-existed
series
variants,
helping
evaluate
risk
enhanced
future.
Additional
9
individuals
infected
SARS-CoV-2.
This
Fc-independent
enhancement
mediated
divalent
F(ab')2
not
Changed
led
ineffectiveness
WT-induced
Language: Английский
Enhancement of SARS-CoV-2 Infection via Crosslinking of Adjacent Spike Proteins by N-Terminal Domain-Targeting Antibodies
Viruses,
Journal Year:
2023,
Volume and Issue:
15(12), P. 2421 - 2421
Published: Dec. 13, 2023
The
entry
of
SARS-CoV-2
into
host
cells
is
mediated
by
the
interaction
between
spike
receptor-binding
domain
(RBD)
and
angiotensin-converting
enzyme
2
(ACE2).
Certain
human
antibodies,
which
target
N-terminal
(NTD)
at
a
distant
epitope
from
cell
binding
surface,
have
been
found
to
augment
ACE2
enhance
infection.
Notably,
these
antibodies
exert
their
effect
independently
antibody
fragment
crystallizable
(Fc)
region,
distinguishing
mode
action
previously
described
antibody-dependent
infection-enhancing
(ADE)
mechanisms.
Building
upon
previous
hypotheses
experimental
evidence,
we
propose
that
NTD-targeting
(NIEAs)
achieve
through
crosslinking
neighboring
proteins.
In
this
study,
present
refined
structural
models
NIEA
antigen-binding
region
(Fab)–NTD
complexes,
supported
molecular
dynamics
simulations
hydrogen–deuterium
exchange
mass
spectrometry
(HDX-MS).
Furthermore,
provide
direct
evidence
confirming
NTDs
NIEAs.
Collectively,
our
findings
advance
understanding
mechanisms
underlying
NIEAs
impact
on
Language: Английский