bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Дек. 16, 2023
Abstract
Viral
glycoproteins
mediate
entry
into
host
cells,
thereby
dictating
range
and
pathogenesis.
In
addition,
they
constitute
the
principal
target
of
neutralizing
antibody
responses,
making
them
important
antigens
in
vaccine
development.
Recombinant
vesicular
stomatitis
virus
(VSV)
encoding
foreign
can
provide
a
convenient
safe
surrogate
system
to
interrogate
function,
evolution,
antigenicity
viral
from
viruses
that
are
difficult
manipulate
or
those
requiring
high
biosafety
levels
containment.
However,
production
recombinant
VSV
be
technically
challenging.
this
work,
we
present
an
efficient
robust
plasmid-based
for
glycoproteins.
We
validate
using
different
families,
including
arenaviruses,
coronaviruses,
hantaviruses,
as
well
highlight
their
utility
studying
effects
mutations
on
fitness.
Overall,
methods
described
herein
facilitate
study
both
native
serve
basis
VSV-based
vaccines.
Viruses,
Год журнала:
2024,
Номер
16(10), С. 1641 - 1641
Опубликована: Окт. 21, 2024
Vesicular
stomatitis
virus
(VSV)
is
a
prototype
RNA
that
has
been
instrumental
in
advancing
our
understanding
of
viral
molecular
biology
and
applications
vaccine
development,
cancer
therapy,
antiviral
screening,
more.
Current
VSV
genome
plasmids
for
purchase
or
contract
services
provide
limited
options
modification,
restricted
to
predefined
cloning
sites
insert
locations.
Improved
methods
tools
engineer
will
unlock
further
insights
into
long-standing
virology
questions
new
opportunities
innovative
therapies.
Here,
we
report
the
design
construction
full-length
genome.
The
11,161
base
pair
synthetic
(synVSV)
was
assembled
from
four
modularized
DNA
fragments.
Following
rescue
titration,
phenotypic
analysis
showed
no
significant
differences
between
natural
viruses.
To
demonstrate
utility
platform,
then
engineered
with
foreign
glycoprotein,
common
use
case
studying
entry
developing
anti-virals.
show
freedom
afforded
by
this
modified
rearranging
gene
order,
switching
positions
VSV-P
VSV-M
genes.
This
work
represents
technical
advance,
providing
flexible,
cost-efficient
platform
rapid
genomes,
facilitating
development
Viruses,
Год журнала:
2022,
Номер
14(9), С. 2031 - 2031
Опубликована: Сен. 13, 2022
Mammalian
seminal
plasma
contains
a
multitude
of
bioactive
components,
including
lipids,
glucose,
mineral
elements,
metabolites,
proteins,
cytokines,
and
growth
factors,
with
various
functions
during
insemination
fertilization.
The
protein
PDC-109
is
one
the
major
soluble
components
bovine
ejaculate
crucially
important
for
sperm
motility,
capacitation,
acrosome
reaction.
A
hitherto
underappreciated
function
its
anti-microbial
antiviral
activity,
which
may
limit
sexual
transmission
infectious
diseases
intercourse.
We
have
recently
discovered
that
inhibits
membrane
fusion
activity
influenza
virus
particles
significantly
impairs
viral
infections
at
micromolar
concentrations.
Here
we
investigated
whether
restricted
to
Influenza
or
if
other
mammalian
viruses
are
similarly
affected.
focused
on
Severe
Acute
Respiratory
Syndrome
Coronavirus-2
(SARS-CoV-2),
etiological
agent
Coronavirus
Disease
19
(COVID-19),
thoroughly
assessing
inhibition
SARS-CoV-2
Spike
(S)-pseudotyped
reporter
particles,
but
also
live-virus
infections.
Consistent
our
previous
publications,
found
significant
inhibition,
albeit
accompanied
by
substantial
cytotoxicity.
However,
using
time-of-addition
experiments
treatment
regimen
enables
suppression
without
affecting
cell
viability.
furthermore
demonstrated
able
impair
mediated
VSV
glycoprotein
(VSVg),
thus
indicating
broad
pan-antiviral
against
multiple
species
families.
Mammalian
seminal
plasma
contains
a
multitude
of
bioactive
components,
including
lipids,
glucose,
mineral
elements,
metabolites,
proteins,
cytokines
and
growth
factors,
with
various
functions
during
insemination
fertilization.
The
protein
PDC-109
is
one
the
major
soluble
components
bovine
ejaculate
crucially
important
for
sperm
motility,
capacitation
acrosome
reaction.
A
hitherto
underappreciated
function
its
anti-microbial
anti-viral
activity,
which
may
limit
sexual
transmission
infectious
diseases
intercourse.
We
have
recently
discovered
that
inhibits
membrane
fusion
activity
influenza
virus
particles
significantly
impairs
viral
infections
at
micromolar
concentrations.
Here
we
investigated
whether
antiviral
restricted
to
Influenza
or
if
other
mammalian
viruses
are
similarly
affected.
focused
on
Severe
Acute
Respiratory
Syndrome
Coronavirus-2
(SARS-CoV-2),
etiological
agent
Coronavirus
Disease
19
(COVID-19),
thoroughly
assessing
inhibition
SARS-CoV-2
Spike
(S)-pseudotyped
reporter
particles,
but
also
live-virus
infections.
Consistent
our
previous
publications
found
significant
inhibition,
albeit
accompanied
by
substantial
cytotoxicity.
Using
time-of-addition
experiments
however,
treatment
regimen
enable
suppression
without
affecting
cell
viability.
furthermore
demonstrated
able
impair
mediated
VSV
glycoprotein
(VSVg)
thus
indicating
broad
pan-antiviral
against
multiple
species
families.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Дек. 16, 2023
Abstract
Viral
glycoproteins
mediate
entry
into
host
cells,
thereby
dictating
range
and
pathogenesis.
In
addition,
they
constitute
the
principal
target
of
neutralizing
antibody
responses,
making
them
important
antigens
in
vaccine
development.
Recombinant
vesicular
stomatitis
virus
(VSV)
encoding
foreign
can
provide
a
convenient
safe
surrogate
system
to
interrogate
function,
evolution,
antigenicity
viral
from
viruses
that
are
difficult
manipulate
or
those
requiring
high
biosafety
levels
containment.
However,
production
recombinant
VSV
be
technically
challenging.
this
work,
we
present
an
efficient
robust
plasmid-based
for
glycoproteins.
We
validate
using
different
families,
including
arenaviruses,
coronaviruses,
hantaviruses,
as
well
highlight
their
utility
studying
effects
mutations
on
fitness.
Overall,
methods
described
herein
facilitate
study
both
native
serve
basis
VSV-based
vaccines.
