bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Дек. 22, 2022
ABSTRACT
It
is
now
established
that
many
viruses
threaten
public
health
establish
condensates
via
phase
transitions
to
complete
their
lifecycles,
and
knowledge
on
such
processes
may
offer
new
strategies
for
antiviral
therapy.
In
the
case
of
influenza
A
virus
(IAV),
liquid
known
as
viral
inclusions,
concentrate
8
distinct
ribonucleoproteins
(vRNPs)
form
IAV
genome
are
viewed
sites
dedicated
assembly
8-partite
genomic
complex.
Despite
not
being
delimited
by
host
membranes,
inclusions
accumulate
membranes
inside
a
result
vRNP
binding
recycling
endocytic
marker
Rab11a,
driver
biogenesis
these
structures.
We
lack
molecular
understanding
how
Rab11a-recycling
endosomes
condensate
specifically
near
endoplasmic
reticulum
(ER)
exit
upon
infection.
show
here
interact
with
ER
fuse,
divide
slide.
uncover
that,
contrary
previous
indications,
reported
reduction
in
activity
regulated
process
rather
than
competition
cellular
resources
involving
novel
role
factor
ATG9A.
infection,
ATG9A
mediates
removal
carrying
vRNPs
from
microtubules.
observe
usage
microtubules
rescued
when
depleted,
which
prevents
condensation
Rab11a
ER.
The
failure
produce
accumulates
cytosol,
reduces
release
infectious
virions.
propose
supports
dynamics
facilitating
formation.
This
work
advances
our
epidemic
pandemic
genomes
formed.
also
reveals
plasticity
pathway
undergo
response
disclosing
roles
beyond
its
classical
involvement
autophagy.
In
biological
systems,
liquid
and
solid-like
biomolecular
condensates
may
contain
the
same
molecules
but
their
behaviour,
including
movement,
elasticity,
viscosity,
is
different
on
account
of
distinct
physicochemical
properties.
As
such,
it
known
that
phase
transitions
affect
function
material
properties
can
be
tuned
by
several
factors
temperature,
concentration,
valency.
It
is,
however,
unclear
if
some
are
more
efficient
than
others
at
regulating
behaviour.
Viral
infections
good
systems
to
address
this
question
as
they
form
de
novo
part
replication
programmes.
Here,
we
used
influenza
A
virus
(IAV)
cytosolic
condensates,
AKA
viral
inclusions,
provide
a
proof
concept
condensate
hardening
via
changes
in
valency
its
components
altering
concentration
or
temperature
cell.
Liquid
IAV
inclusions
hardened
targeting
vRNP
(viral
ribonucleoprotein)
interactions
NP
(nucleoprotein)
oligomerising
molecule,
nucleozin,
both
vitro
vivo
without
affecting
host
proteome
abundance
nor
solubility.
This
study
starting
point
for
understanding
how
pharmacologically
modulate
offer
opportunities
alternative
antiviral
strategies.
Molecular Biology of the Cell,
Год журнала:
2024,
Номер
35(7)
Опубликована: Май 29, 2024
Fluorescent
protein
(FP)
tags
are
extensively
used
to
visualize
and
characterize
the
properties
of
biomolecular
condensates
despite
a
lack
investigation
into
effects
these
on
phase
separation.
Here,
we
characterized
dynamic
µNS,
viral
hypothesized
undergo
separation
main
component
mammalian
orthoreovirus
factories.
Our
interest
in
sequence
determinants
nucleation
process
µNS
led
us
compare
size
density
formed
by
FP::µNS
untagged
protein.
We
found
an
FP-dependent
increase
droplet
density,
which
suggests
that
FP
can
promote
condensation.
To
further
assess
effect
formation,
fused
mutants
show
could
variably
induce
otherwise
noncondensing
proteins.
By
comparing
fluorescent
constructs
with
identified
mNeonGreen
as
least
artifactual
tag
minimally
perturbed
These
results
some
more
suitable
for
visualizing
characterizing
minimal
experimental
artifacts.
The EMBO Journal,
Год журнала:
2024,
Номер
43(2), С. 277 - 303
Опубликована: Янв. 2, 2024
Abstract
Biomolecular
condensates
(BMCs)
play
important
roles
in
diverse
biological
processes.
Many
viruses
form
BMCs
which
have
been
implicated
various
functions
critical
for
the
productive
infection
of
host
cells.
The
adenovirus
L1-52/55
kilodalton
protein
(52K)
was
recently
shown
to
viral
that
coordinate
genome
packaging
and
capsid
assembly.
Although
packaging,
we
do
not
know
how
are
regulated
during
infection.
Here
show
phosphorylation
serine
residues
28
75
within
N-terminal
intrinsically
disordered
region
52K
modulates
vitro
cells,
promoting
liquid-like
properties.
Furthermore,
demonstrate
promotes
production
infectious
progeny
particles.
Collectively,
our
findings
provide
insights
into
condensate
properties
maintained
a
state
conducive
their
function
production.
In
addition,
implications
antiviral
strategies
aimed
at
targeting
regulation
limit
multiplication.
PLoS Biology,
Год журнала:
2023,
Номер
21(11), С. e3002290 - e3002290
Опубликована: Ноя. 20, 2023
It
is
now
established
that
many
viruses
threaten
public
health
establish
condensates
via
phase
transitions
to
complete
their
lifecycles,
and
knowledge
on
such
processes
may
offer
new
strategies
for
antiviral
therapy.
In
the
case
of
influenza
A
virus
(IAV),
liquid
known
as
viral
inclusions,
concentrate
8
distinct
ribonucleoproteins
(vRNPs)
form
IAV
genome
are
viewed
sites
dedicated
assembly
8-partite
genomic
complex.
Despite
not
being
delimited
by
host
membranes,
inclusions
accumulate
membranes
inside
a
result
vRNP
binding
recycling
endocytic
marker
Rab11a,
driver
biogenesis
these
structures.
We
lack
molecular
understanding
how
Rab11a-recycling
endosomes
condensate
specifically
near
endoplasmic
reticulum
(ER)
exit
upon
infection.
show
here
interact
with
ER
fuse,
divide,
slide.
uncover
that,
contrary
previous
indications,
reported
reduction
in
activity
regulated
process
rather
than
competition
cellular
resources
involving
novel
role
factor
ATG9A.
infection,
ATG9A
mediates
removal
carrying
vRNPs
from
microtubules.
observe
usage
microtubules
rescued
when
depleted,
which
prevents
condensation
Rab11a
ER.
The
failure
produce
accumulates
cytosol
reduces
release
infectious
virions.
propose
supports
dynamics
facilitating
formation.
This
work
advances
our
epidemic
pandemic
genomes
formed.
also
reveals
plasticity
undergo
response
disclosing
roles
beyond
its
classical
involvement
autophagy.
PLoS Pathogens,
Год журнала:
2024,
Номер
20(3), С. e1012060 - e1012060
Опубликована: Март 5, 2024
The
recent
discovery
of
Hepatitis
D
(HDV)
-like
viruses
across
a
wide
range
taxa
led
to
the
establishment
Kolmioviridae
family.
Recent
studies
suggest
that
kolmiovirids
can
be
satellites
other
than
B
virus
(HBV),
challenging
strict
HBV/HDV-association
dogma.
Studying
whether
are
able
replicate
in
any
animal
cell
they
enter
is
essential
assess
their
zoonotic
potential.
Here,
we
compared
replication
three
kolmiovirids:
HDV,
rodent
(RDeV)
and
snake
(SDeV)
deltavirus
vitro
vivo
.
We
show
SDeV
has
narrowest
RDeV
broadest
host
range.
High
resolution
imaging
cells
persistently
replicating
these
revealed
nuclear
viral
hubs
with
peculiar
RNA-protein
organization.
Finally,
hydrodynamic
delivery
replicons
showed
both
HDV
RDeV,
but
not
SDeV,
efficiently
mouse
liver,
forming
massive
hubs.
Our
comparative
analysis
lays
foundation
for
specific
factors
controlling
host-shifting.
Microbes and Infection,
Год журнала:
2024,
Номер
26(8), С. 105402 - 105402
Опубликована: Авг. 8, 2024
During
a
viral
infection,
several
membraneless
compartments
with
liquid
properties
are
formed.
They
can
be
of
origin
concentrating
proteins
and
nucleic
acids,
harboring
essential
stages
the
cycle,
or
cellular
containing
components
involved
in
innate
immunity.
This
is
paradigm
shift
our
understanding
replication
interaction
between
viruses
