Caspase-1/11 Controls Zika Virus Replication in Astrocytes by Regulating Glycolytic Metabolism
Abstract
The
Zika
virus
(ZIKV)
poses
a
significant
threat
due
to
its
association
with
severe
neurological
complications,
particularly
during
pregnancy.
Although
viruses
exhibit
tropism
for
neural
cells,
including
astrocytes,
the
role
of
these
cells
in
controlling
ZIKV
replication
remains
unclear.
In
this
study,
we
demonstrated
that
induces
caspase-1
activation
primary
astrocytes
despite
absence
classical
signs
inflammasome
activation.
Caspase-1/11−/−
heightened
permissiveness
viral
replication,
accompanied
by
overactivation
glycolytic
metabolism.
Inhibition
glycolysis
reversed
susceptibility
caspase-1/11−/−
infection.
Protein
network
analysis
revealed
mTORC
as
link
between
proteins
involved
and
caspase-1,
inhibition
also
suppressed
replication.
Furthermore,
found
impact
caspase-1/11
on
is
dependent
pyruvate
transport
mitochondria
emphasizing
mTORC/glycolytic
pathway/pyruvate
axis
caspase-1/11-mediated
control
ZIKV.
Overall,
our
findings
elucidate
caspase-1/11-dependent
microbicidal
mechanism
providing
insights
into
potential
therapeutic
targets
Research Square (Research Square), Год журнала: 2024, Номер unknown
Опубликована: Май 2, 2024
Язык: Английский
