PLoS Pathogens,
Год журнала:
2017,
Номер
13(8), С. e1006570 - e1006570
Опубликована: Авг. 21, 2017
The
dynamics
and
regulation
of
HIV-1
nuclear
import
its
intranuclear
movements
after
have
not
been
studied.
To
elucidate
these
essential
post-entry
events,
we
labeled
viral
complexes
with
two
fluorescently
tagged
virion-incorporated
proteins
(APOBEC3F
or
integrase),
analyzed
the
envelope
(NE)
docking,
import,
in
living
cells.
We
observed
that
exhibit
unusually
long
NE
residence
times
(1.5±1.6
hrs)
compared
to
most
cellular
cargos,
which
are
imported
into
nuclei
within
milliseconds.
Furthermore,
requires
capsid
(CA)
pore
protein
Nup358,
results
significant
loss
CA,
indicating
one
core
uncoating
steps
occurs
during
import.
Our
showed
CA-Cyclophilin
A
interaction
regulates
by
delaying
time
docking
as
well
transport
through
pore,
but
blocking
reverse
transcription
has
no
effect
on
kinetics
also
visualized
translocation
docked
at
nucleus
their
determined
exhibited
a
brief
fast
phase
(<9
min),
followed
slow
lasting
several
hours.
comparison
movement
those
proviral
sites
supports
hypothesis
quickly
tether
chromatin
near
integration
both
wild-type
cells
LEDGF/p75
was
deleted
using
CRISPR/cas9,
tethering
interactions
do
require
LEDGF/p75.
These
studies
provide
novel
insights
complex-NE
association,
uncoating,
precede
site
selection.
Leukemia,
Год журнала:
2018,
Номер
32(7), С. 1529 - 1541
Опубликована: Март 22, 2018
Viral
vectors
provide
an
efficient
means
for
modification
of
eukaryotic
cells,
and
their
use
is
now
commonplace
in
academic
laboratories
industry
both
research
clinical
gene
therapy
applications.
Lentiviral
vectors,
derived
from
the
human
immunodeficiency
virus,
have
been
extensively
investigated
optimized
over
past
two
decades.
Third-generation,
self-inactivating
lentiviral
recently
used
multiple
trials
to
introduce
genes
into
hematopoietic
stem
cells
correct
primary
immunodeficiencies
hemoglobinopathies.
These
also
mature
T
generate
immunity
cancer
through
delivery
chimeric
antigen
receptors
(CARs)
or
cloned
T-cell
receptors.
CAR
therapies
engineered
using
demonstrated
noteworthy
success
patients
with
B-cell
malignancies
leading
regulatory
approval
first
genetically
cellular
vectors.
In
this
review,
we
discuss
several
aspects
that
will
be
interest
clinicians,
including
overview
vector
development,
current
uses
viral
as
cancers,
large-scale
manufacturing
long-term
follow-up
treated
products.
Cell,
Год журнала:
2021,
Номер
184(4), С. 1032 - 1046.e18
Опубликована: Фев. 1, 2021
Human
immunodeficiency
virus
(HIV-1)
remains
a
major
health
threat.
Viral
capsid
uncoating
and
nuclear
import
of
the
viral
genome
are
critical
for
productive
infection.
The
size
HIV-1
is
generally
believed
to
exceed
diameter
pore
complex
(NPC),
indicating
that
has
occur
prior
import.
Here,
we
combined
correlative
light
electron
microscopy
with
subtomogram
averaging
capture
structural
status
reverse
transcription-competent
complexes
in
infected
T
cells.
We
demonstrated
NPC
cellulo
sufficient
apparently
intact,
cone-shaped
capsids.
Subsequent
import,
detected
disrupted
empty
fragments,
replication
occurs
by
breaking
open,
not
disassembly
into
individual
subunits.
Our
data
directly
visualize
key
step
enhance
our
mechanistic
understanding
life
cycle.
Proceedings of the National Academy of Sciences,
Год журнала:
2020,
Номер
117(10), С. 5486 - 5493
Опубликована: Фев. 24, 2020
Significance
For
several
decades,
retroviral
core
uncoating
has
been
thought
to
occur
in
the
cytoplasm
coordination
with
reverse
transcription,
and
while
some
recent
studies
have
concluded
that
HIV-1
occurs
at
nuclear
envelope
during
import,
none
nucleus.
Here,
we
developed
methods
study
by
direct
labeling
quantification
of
viral
capsid
protein
associated
infectious
cores
produced
transcriptionally
active
proviruses.
We
find
nuclei
infected
cells
are
largely
intact
uncoat
near
their
integration
sites
just
before
integration.
These
unexpected
findings
fundamentally
change
our
understanding
postentry
replication
events.
Annual Review of Biophysics,
Год журнала:
2019,
Номер
48(1), С. 515 - 536
Опубликована: Апрель 3, 2019
Nuclear
pore
complexes
(NPCs)
mediate
nucleocytoplasmic
exchange.
They
are
exceptionally
large
protein
that
fuse
the
inner
and
outer
nuclear
membranes
to
form
channels
across
envelope.
About
30
different
components,
termed
nucleoporins,
assemble
in
multiple
copies
into
an
intricate
cylindrical
architecture.
Here,
we
review
our
current
knowledge
of
structure
nucleoporins
how
those
come
together
situ.
We
delineate
architectural
principles
on
several
hierarchical
organization
levels,
including
isoforms,
posttranslational
modifications,
higher-order
oligomerization
nucleoporin
subcomplexes.
discuss
cells
exploit
this
modularity
faithfully
NPCs.
Nuclear
entry
of
HIV-1
replication
complexes
through
intact
nuclear
pore
is
critical
for
successful
infection.
The
host
protein
cleavage-and-polyadenylation-specificity-factor-6
(CPSF6)
has
been
implicated
in
different
stages
early
replication.
Applying
quantitative
microscopy
reverse-transcription
and
pre-integration-complexes
(RTC/PIC),
we
show
that
CPSF6
strongly
recruited
to
but
absent
from
cytoplasmic
RTC/PIC
primary
human
macrophages.
Depletion
or
lack
binding
led
accumulation
subviral
at
the
envelope
macrophages
reduced
infectivity.
Two-color
stimulated-emission-depletion
indicated
under
these
circumstances
are
retained
inside
undergo
CA-multimer
dependent
clustering
adjacent
basket.
We
propose
mediated
by
consecutive
Nup153
hexameric
CA
lattice.
Advanced Materials,
Год журнала:
2018,
Номер
30(45)
Опубликована: Сен. 25, 2018
Abstract
To
improve
human
immunodeficiency
virus
(HIV)
treatment
and
prevention,
therapeutic
strategies
that
can
provide
effective
broad‐spectrum
neutralization
against
viral
infection
are
highly
desirable.
Inspired
by
recent
advances
of
cell‐membrane
coating
technology,
herein,
plasma
membranes
CD4
+
T
cells
collected
coated
onto
polymeric
cores.
The
resulting
T‐cell‐membrane‐coated
nanoparticles
(denoted
as
“TNPs”)
inherit
cell
surface
antigens
critical
for
HIV
binding,
such
receptor
CCR5
or
CXCR4
coreceptors.
TNPs
act
decoys
attack
neutralize
diverting
the
viruses
away
from
their
intended
host
targets.
This
decoy
strategy,
which
simulates
functions
rather
than
directly
suppressing
replication
machinery,
has
potential
to
overcome
genetic
diversity
while
not
eliciting
high
selective
pressure.
In
this
study,
it
is
demonstrated
selectively
bind
with
gp120,
a
key
envelope
glycoprotein
HIV,
inhibit
gp120‐induced
killing
bystander
cells.
Furthermore,
when
added
viruses,
effectively
peripheral
mononuclear
blood
human‐monocyte‐derived
macrophages
in
dose‐dependent
manner.
Overall,
leveraging
natural
functions,
show
great
new
agent
infection.
