International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(5), С. 2621 - 2621
Опубликована: Фев. 23, 2024
Combination
antiretroviral
therapy
(cART)
has
significantly
improved
the
prognosis
of
individuals
living
with
human
immunodeficiency
virus
(HIV).
Acquired
syndrome
transformed
from
a
fatal
disease
to
treatable
chronic
infection.
Currently,
effective
and
safe
anti-HIV
drugs
are
available.
Although
cART
can
reduce
viral
production
in
body
patient
below
detection
limit,
it
cannot
eliminate
HIV
provirus
integrated
into
host
cell
genome;
hence,
will
be
produced
again
after
discontinuation.
Therefore,
research
cure
(or
remission)
for
been
widely
conducted.
In
this
review,
we
focus
on
drug
development
targeting
cells
latently
infected
assess
progress
including
our
current
studies,
particularly
terms
“Shock
Kill”,
“Block
Lock”
strategies.
Biomolecules,
Год журнала:
2025,
Номер
15(3), С. 378 - 378
Опубликована: Март 5, 2025
Antiretroviral
therapy
(ART)
can
effectively
suppress
the
replication
of
human
immunodeficiency
virus
(HIV),
but
it
cannot
completely
eradicate
virus.
The
persistent
existence
HIV
reservoir
is
a
major
obstacle
in
quest
for
cure.
To
date,
there
have
been
total
seven
cured
cases
worldwide.
These
patients
all
cleared
while
undergoing
allogeneic
stem
cell
transplantation
(allo-HSCT)
hematological
malignancies.
However,
these
cases,
specific
mechanism
by
which
allo-HSCT
leads
to
eradication
remains
unclear,
so
necessary
conduct
an
in-depth
analysis.
Due
difficulty
obtaining
donors
and
risks
associated
with
transplantation,
this
treatment
method
not
applicable
patients.
There
still
need
explore
new
strategies.
In
recent
years,
emerging
therapies
such
as
neutralizing
antibody
immunotherapy,
chimeric
antigen
receptor
T
(CAR-T)
therapy,
gene
editing,
antiviral
targeting
attracted
wide
attention
due
their
ability
inhibit
replication.
This
article
first
elaborates
on
nature
reservoir,
then
deeply
explores
modalities
potential
success
factors
finally
discusses
current
novel
methods,
hoping
provide
comprehensive
feasible
strategies
achieving
cure
HIV.
Journal of Virology,
Год журнала:
2025,
Номер
unknown
Опубликована: Июнь 4, 2025
ABSTRACT
Antiretroviral
therapy
(ART)
suppresses
HIV
replication
in
people
living
with
(PWH),
but
a
persistent
population
of
reservoir
cells
prevents
cure.
Reservoir
are
mostly
anatomically
dispersed,
latently
infected
CD4+
T
harboring
one
copy
chromosomally
integrated,
replication-competent
proviral
DNA.
Despite
their
low
frequency
(0.01%–0.1%)
among
and
the
quiescence
most
genetically
intact
proviruses,
viremia
usually
recurs
within
weeks
after
ART
cessation.
When
PWH
not
on
ART,
is
sustained
through
viral
infection
cell
proliferation.
During
suppressive
persist
via
mechanisms
sustaining
uninfected
including
antigen-responsive
homeostatic
clonal
proliferation,
programmed
death,
subset
differentiation.
Rates
proliferation
death
must
exist
quasi-equilibrium
to
explain
limited
change
volume
over
decades
rarity
cancers
or
lymphoproliferative
disorders
emerging
from
cells.
Some
under
additional
selection
forces
during
illustrated
by
slightly
higher
clearance
rates
versus
replication-defective
DNA
gradual
transition
less
transcriptionally
active
more
reservoir.
While
small
meaningful
percentage
negatively
selected
due
lytic
elimination
adaptive
immune
responses,
occurs
independently
Given
that
often
passenger
cells,
targeted
differentiation
may
be
viable
therapeutic
targets
for
curative
interventions.
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Июль 19, 2024
Abstract
An
influenza
vaccine
approach
that
overcomes
the
problem
of
viral
sequence
diversity
and
provides
long-lived
heterosubtypic
protection
is
urgently
needed
to
protect
against
pandemic
viruses.
Here,
determine
if
lung-resident
effector
memory
T
cells
induced
by
cytomegalovirus
(CMV)-vectored
vaccines
expressing
conserved
internal
antigens
could
lethal
challenge,
we
immunize
Mauritian
cynomolgus
macaques
(MCM)
with
CMV
(CyCMV)
H1N1
1918
M1,
NP,
PB1
(CyCMV/Flu),
challenge
heterologous,
aerosolized
avian
H5N1
influenza.
All
six
unvaccinated
MCM
died
seven
days
post
infection
acute
respiratory
distress,
while
54.5%
(6/11)
CyCMV/Flu-vaccinated
survived.
Survival
correlates
magnitude
influenza-specific
CD4
+
prior
challenge.
These
data
demonstrate
targeting
proteins
can
highly
pathogenic
heterologous
support
further
exploration
cell-based
for
universal
development.
Current
antiretroviral
therapy
(ART)
regimens
efficiently
limit
HIV
replication,
thereby
improving
life
expectancy
of
people
living
with
HIV,
but
also
cause
metabolic
side
effects.
The
ongoing
obesity
epidemic
has
resulted
in
more
comorbidities
at
the
time
infection,
yet
impact
pre-existing
dysregulation
on
infection
sequelae
and
response
to
ART
is
unclear.
Here,
investigate
preexisting
insulin
resistance
acute
subsequent
long-term
ART,
we
infected
a
cohort
lean
obese
adult
male
macaques
SIV
administered
ART.
responses
were
similar
respect
plasma
cell-associated
viral
loads,
drug
levels
tissues,
SIV-specific
immune
responses,
adipose
tissue
islet
morphology,
colon
inflammation,
baseline
differences
between
groups
largely
maintained.
Both
exhibited
striking
depletion
CD4+
T
cells
from
that
did
not
recover
However,
differential
observed
for
body
weight,
omental
adipocyte
size,
adiponectin/leptin
ratio,
marker
cardiometabolic
risk.
Thus,
had
limited
effects
multiple
while
several
factors
underlie
influenced
by
prior
resistance.
These
studies
provide
foundation
future
investigations
into
efficacy
adjunct
therapies
such
as
metformin
glucagon-like
peptide-1
receptor
agonists
prevention
HIV.
PLoS Pathogens,
Год журнала:
2023,
Номер
19(9), С. e1011676 - e1011676
Опубликована: Сен. 25, 2023
Sustainable
HIV
remission
after
antiretroviral
therapy
(ART)
withdrawal,
or
post-treatment
control
(PTC),
remains
a
top
priority
for
treatment.
We
observed
surprising
PTC
in
an
MHC-haplomatched
cohort
of
MHC-M3+
SIVmac239+
Mauritian
cynomolgus
macaques
(MCMs)
initiated
on
ART
at
two
weeks
post-infection
(wpi).
None
the
MCMs
possessed
MHC
haplotypes
previously
associated
with
SIV
control.
For
six
months
we
undetectable
transient
viremia
seven
eight
MCMs,
despite
detecting
replication
competent
using
quantitative
viral
outgrowth
assays.
In
vivo
depletion
CD8α+
cells
induced
rebound
all
animals,
indicating
was
mediated,
least
part,
by
cells.
With
intact
proviral
DNA
assays,
found
that
had
significantly
smaller
reservoirs
wpi
than
identically
infected
rhesus
macaques,
population
rarely
develops
PTC.
similarly
small
reservoir
among
additional
SIV+
which
wpi,
some
whom
exhibited
rebound.
These
results
suggest
unusually
is
hallmark
MCMs.
By
evaluating
immunological
differences
between
did
and
not
rebound,
identified
reduced
frequency
CD4+
CD8+
lymphocyte
subsets
expressing
exhaustion
markers.
Together,
these
combination
immune-mediated
virus
suppression
contribute
to
Further,
defining
immunologic
mechanisms
engender
this
model
may
identify
therapeutic
targets
inducing
durable
humans.
