During
HIV-1
maturation,
the
matrix
(MA)
lattice
underlying
viral
membrane
undergoes
a
structural
rearrangement,
and
newly
released
capsid
(CA)
protein
forms
mature
CA.
While
it
is
well
established
that
CA
formation
essential
for
particle
infectivity,
functional
role
of
MA
maturation
remains
unclear.
Here,
we
examine
an
triple
mutant,
L20K/E73K/A82T,
which,
despite
replicating
similarly
to
wild-type
(WT)
in
some
cell
lines,
exhibits
distinct
biochemical
behaviors
suggest
altered
MA-MA
interactions.
Cryo–electron
tomography
with
subtomogram
averaging
reveals
that,
although
immature
L20K/E73K/A82T
virions
closely
resembles
WT,
lack
detectable
lattice.
All-atom
molecular
dynamics
simulations
this
absence
results
from
destabilized
inter-trimer
interactions
mutant
virions.
These
findings
ordered,
membrane-associated
not
providing
insights
into
requirements
generation
infectious
particles.
Proceedings of the National Academy of Sciences,
Год журнала:
2023,
Номер
120(28)
Опубликована: Июль 5, 2023
HIV-1
assembly
occurs
at
the
inner
leaflet
of
plasma
membrane
(PM)
in
highly
ordered
microdomains.
The
size
and
stability
microdomains
is
regulated
by
activity
sphingomyelin
hydrolase
neutral
sphingomyelinase
2
(nSMase2)
that
localized
primarily
to
PM.
In
this
study,
we
demonstrate
pharmacological
inhibition
or
depletion
nSMase2
HIV-1-producer
cells
results
a
block
processing
major
viral
structural
polyprotein
Gag
production
morphologically
aberrant,
immature
particles
with
severely
impaired
infectivity.
We
find
disruption
also
inhibits
maturation
infectivity
other
primate
lentiviruses
HIV-2
simian
immunodeficiency
virus,
has
modest
no
effect
on
nonprimate
equine
infectious
anemia
virus
feline
gammaretrovirus
murine
leukemia
virus.
These
studies
key
role
for
particle
morphogenesis
maturation.
Viruses,
Год журнала:
2024,
Номер
16(9), С. 1423 - 1423
Опубликована: Сен. 6, 2024
HIV-1
virion
maturation
is
an
essential
step
in
the
viral
replication
cycle
to
produce
infectious
virus
particles.
Gag
and
Gag-Pol
polyproteins
are
assembled
at
plasma
membrane
of
virus-producer
cells
bud
from
it
extracellular
compartment.
The
newly
released
progeny
virions
initially
immature
noninfectious.
However,
once
polyprotein
cleaved
by
protease
virions,
mature
capsid
proteins
assemble
form
fullerene
core.
This
core,
harboring
two
copies
genomic
RNA,
transforms
morphology
into
morphological
transformation
referred
as
maturation.
Virion
influences
distribution
Env
glycoprotein
on
surface
induces
conformational
changes
necessary
for
subsequent
interaction
with
CD4
receptor.
Several
host
factors,
including
like
cyclophilin
A,
metabolites
such
IP6,
lipid
rafts
containing
sphingomyelins,
have
been
demonstrated
influence
review
article
delves
processes
recruitment,
emphasis
role
cell
factors
environmental
conditions.
Additionally,
we
discuss
microscopic
technologies
assessing
development
current
antivirals
specifically
targeting
this
critical
replication,
offering
long-acting
therapeutic
options.
Viruses,
Год журнала:
2025,
Номер
17(3), С. 364 - 364
Опубликована: Март 3, 2025
HIV
is
a
lentivirus
characterized
by
its
cone
shaped
mature
core.
Visualization
and
structural
examination
of
requires
the
purification
virions
to
high
concentrations.
The
yield
integrity
these
are
crucial
for
ensuring
uniform
representation
all
viral
particles
in
subsequent
analyses.
In
this
study,
we
present
method
which
minimizes
forces
applied
while
maximizing
efficiency
collection.
This
method,
relies
on
virion
sedimentation
simulations,
allows
us
capture
between
1000
5000
released
from
individual
HEK293
cells
after
transfection
with
NL4.3
backbone.
We
utilized
approach
investigate
core
formation
several
constructs:
pNL4-3(RT:D185A&D186A)
an
inactive
reverse
transcriptase,
NL4.3(IN:
V165A&R166A)
type-II
integrase
mutation,
NL4.3(Ψ:
Δ(105–278)&Δ(301–332))
featuring
edited
Ψ
packaging
signal.
Notably,
displayed
mixed
population,
comprising
immature
virions,
empty
cores,
cores
detectable
internal
density.
Conversely,
derived
exhibited
type
II
mutant
phenotype
RNP
density
localized
around
consistent
previous
studies.
contrast,
containing
suggest
that
simulations
developed
study
can
facilitate
characterization
enveloped
viruses.
During
HIV-1
maturation,
the
matrix
(MA)
lattice
underlying
viral
membrane
undergoes
a
structural
rearrangement,
and
newly
released
capsid
(CA)
protein
forms
mature
CA.
While
it
is
well
established
that
CA
formation
essential
for
particle
infectivity,
functional
role
of
MA
maturation
remains
unclear.
Here,
we
examine
an
triple
mutant,
L20K/E73K/A82T,
which,
despite
replicating
similarly
to
wild-type
(WT)
in
some
cell
lines,
exhibits
distinct
biochemical
behaviors
suggest
altered
MA-MA
interactions.
Cryo–electron
tomography
with
subtomogram
averaging
reveals
that,
although
immature
L20K/E73K/A82T
virions
closely
resembles
WT,
lack
detectable
lattice.
All-atom
molecular
dynamics
simulations
this
absence
results
from
destabilized
inter-trimer
interactions
mutant
virions.
These
findings
ordered,
membrane-associated
not
providing
insights
into
requirements
generation
infectious
particles.
