bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 20, 2024
ABSTRACT
The
intricate
interplay
between
+RNA
viruses
and
their
hosts
involves
the
exploitation
of
host
resources
to
build
virus-induced
membranous
replication
organelles
(VROs)
in
cytosol
infected
cells.
Previous
genome-
proteome-wide
approaches
have
identified
numerous
nuclear
proteins,
including
restriction
factors
that
affect
tomato
bushy
stunt
virus
(TBSV).
However,
it
is
currently
unknown
how
cells
mobilize
antiviral
proteins
tombusviruses
manipulate
nuclear-cytoplasmic
communication.
authors
discovered
XPO1/CRM1
exportin
plays
a
central
role
TBSV
plants.
Based
on
knockdown,
chemical
inhibition,
transient
expression
vitro
experiments,
we
show
XPO1
acts
as
cellular
factor
against
TBSV.
recruited
by
p33
protein
into
cytosolic
VROs
via
direct
interaction.
Blocking
nucleocytoplasmic
transport
function
inhibits
delivery
several
resulting
dampened
effects.
co-opted
actin
network
critical
for
deliver
activities.
We
XPO1-delivered
accumulate
vir-condensates
associated
with
VROs.
Altogether,
emerging
theme
complex:
propose
vir-condensate
serves
battleground
supremacy
controlling
infection.
It
seems
balance
pro-viral
within
could
be
major
determining
susceptibility.
conclude
cargos
are
key
players
communication
during
replication.
Significance
Tomato
(TBSV),
similar
other
(+)RNA
viruses,
replicates
exploits
organellar
membrane
surfaces
viral
represent
sites
shuttle
inhibited
conserved
interaction
nod,
which
propelled
restricted
delivered
provided
inhibitory
functions
condensates
VRO-associated
condensate
hub
implications
its
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Авг. 25, 2023
Many
viral
proteins
form
biomolecular
condensates
via
liquid-liquid
phase
separation
(LLPS)
to
support
replication
and
evade
host
antiviral
responses,
thus,
they
are
potential
targets
for
designing
antivirals.
In
the
case
of
non-enveloped
positive-sense
RNA
viruses,
forming
such
is
unclear
less
understood.
Human
noroviruses
(HuNoV)
viruses
that
cause
epidemic
sporadic
gastroenteritis
worldwide.
Here,
we
show
RNA-dependent-RNA
polymerase
(RdRp)
pandemic
GII.4
HuNoV
forms
distinct
exhibit
all
signature
properties
LLPS
with
sustained
activity
capability
recruiting
components
essential
replication.
We
formed
in
HuNoV-infected
human
intestinal
enteroid
cultures
sites
genome
Our
studies
demonstrate
formation
separated
as
factories
a
virus,
which
plausibly
an
effective
mechanism
dynamically
isolate
RdRp
replicating
genomic
from
interfering
ribosomal
translation
same
RNA.
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 10, 2024
Abstract
Chemical
management
of
crop
failures
caused
by
plant
viruses
poses
serious
challenges
in
agricultural
chemistry.
Recently,
phase
separation
has
emerged
as
a
key
role
the
viral
lifecycle,
with
discovery
corresponding
small
molecule
inhibitors
medical
field
sparking
significant
interest.
However,
applicability
this
promising
antiviral
tactic
for
protection
remains
largely
unknown.
Herein,
we
have
demonstrated
that
aggregation
tomato
spotted
wilt
virus
(TSWV)
nucleocapsid
protein
(N)
is
regulated
RNA-induced
separation,
and
disclosed
new
rationally
designed
inhibitor
Z9.
Z9
capable
binding
to
TSWV
N
at
R94
Y184
sites,
preventing
assembly
RNA
into
aggregated
ribonucleoproteins
through
separation.
Mutations
sites
substantially
diminish
colocalization
between
processing
bodies,
interfering
normal
interaction
RNA.
This
study
provides
opportunities
separation-based
anti-plant
virus
strategies.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 20, 2024
ABSTRACT
The
intricate
interplay
between
+RNA
viruses
and
their
hosts
involves
the
exploitation
of
host
resources
to
build
virus-induced
membranous
replication
organelles
(VROs)
in
cytosol
infected
cells.
Previous
genome-
proteome-wide
approaches
have
identified
numerous
nuclear
proteins,
including
restriction
factors
that
affect
tomato
bushy
stunt
virus
(TBSV).
However,
it
is
currently
unknown
how
cells
mobilize
antiviral
proteins
tombusviruses
manipulate
nuclear-cytoplasmic
communication.
authors
discovered
XPO1/CRM1
exportin
plays
a
central
role
TBSV
plants.
Based
on
knockdown,
chemical
inhibition,
transient
expression
vitro
experiments,
we
show
XPO1
acts
as
cellular
factor
against
TBSV.
recruited
by
p33
protein
into
cytosolic
VROs
via
direct
interaction.
Blocking
nucleocytoplasmic
transport
function
inhibits
delivery
several
resulting
dampened
effects.
co-opted
actin
network
critical
for
deliver
activities.
We
XPO1-delivered
accumulate
vir-condensates
associated
with
VROs.
Altogether,
emerging
theme
complex:
propose
vir-condensate
serves
battleground
supremacy
controlling
infection.
It
seems
balance
pro-viral
within
could
be
major
determining
susceptibility.
conclude
cargos
are
key
players
communication
during
replication.
Significance
Tomato
(TBSV),
similar
other
(+)RNA
viruses,
replicates
exploits
organellar
membrane
surfaces
viral
represent
sites
shuttle
inhibited
conserved
interaction
nod,
which
propelled
restricted
delivered
provided
inhibitory
functions
condensates
VRO-associated
condensate
hub
implications
its
