Brief Histories of Retroviral Integration Research and Associated International Conferences
Viruses,
Год журнала:
2024,
Номер
16(4), С. 604 - 604
Опубликована: Апрель 13, 2024
The
field
of
retroviral
integration
research
has
a
long
history
that
started
with
the
provirus
hypothesis
and
subsequent
discoveries
reverse
transcriptase
integrase
enzymes.
Because
both
enzymes
are
essential
for
replication,
they
became
valued
targets
in
effort
to
discover
effective
compounds
inhibit
HIV-1
replication.
In
2007,
first
strand
transfer
inhibitor
was
licensed
clinical
use,
subsequently
approved
second-generation
inhibitors
now
commonly
co-formulated
treat
people
living
HIV.
International
meetings
specifically
focused
on
convened
1995,
this
paper
is
part
Viruses
Special
Issue
7th
Conference
Retroviral
Integration,
which
held
Boulder
Colorado
summer
2023.
Herein,
we
overview
key
historical
developments
field,
especially
as
pertain
development
drug
class.
Starting
from
mid-1990s,
advancements
presented
through
lens
international
conferences.
Our
highlights
impact
regularly
scheduled,
subject-specific
can
have
community-building
and,
result,
field-specific
collaborations
scientific
advancements.
Язык: Английский
Population-based nanopore sequencing of the HIV-1 pangenome to identify drug resistance mutations
Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Май 27, 2024
HIV-1
drug
resistance
genotypic
tests
have
primarily
been
performed
by
Sanger
sequencing
of
gene
segments
encoding
different
target
proteins.
Since
the
number
targets
has
increased
with
addition
a
new
class
antiretroviral
drugs,
simple
high-throughput
system
for
assessing
nucleotide
sequences
throughout
genome
is
required.
Here,
we
developed
solution
using
nanopore
viral
pangenomes
amplified
PCR.
Benchmark
molecular
clones
demonstrated
an
accuracy
up
to
99.9%.
In
addition,
validation
our
protocol
in
106
clinical
samples
high
concordance
and
tropism
genotypes
(92.5%
98.1%,
respectively)
between
sequencing-based
results
archived
determinations
made
based
on
data.
These
suggest
that
approach
will
be
powerful
comprehensive
survey
mutations
settings.
Язык: Английский
Comprehensive Database of HIV Mutations Selected During Antiretroviral In Vitro Passage Experiments
Antiviral Research,
Год журнала:
2024,
Номер
230, С. 105988 - 105988
Опубликована: Авг. 16, 2024
In
vitro
passage
experiments
are
crucial
to
the
development
of
antiretroviral
(ARV)
drugs.
Язык: Английский
The miRNomics of antiretroviral therapy-induced obesity
Functional & Integrative Genomics,
Год журнала:
2025,
Номер
25(1)
Опубликована: Апрель 5, 2025
Язык: Английский
Structural maturation of the matrix lattice is not required for HIV-1 particle infectivity
Science Advances,
Год журнала:
2025,
Номер
11(19)
Опубликована: Май 9, 2025
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.
Язык: Английский
Structural maturation of the matrix lattice is not required for HIV-1 particle infectivity
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Дек. 23, 2024
Abstract
HIV-1
assembly
is
initiated
by
the
binding
of
Gag
polyproteins
to
inner
leaflet
plasma
membrane,
mediated
myristylated
matrix
(MA)
domain
Gag.
Subsequent
membrane
binding,
oligomerizes
and
buds
as
an
immature,
non-infectious
virus
particle,
which,
upon
cleavage
precursor
viral
protease,
transforms
into
a
mature,
infectious
virion.
During
maturation,
MA
lattice
underlying
undergoes
structural
rearrangement
newly
released
capsid
(CA)
protein
forms
mature
that
encloses
genome.
While
it
well
established
formation
essential
particle
infectivity,
functional
role
maturation
remains
unclear.
Here,
we
examine
triple
mutant,
L20K/E73K/A82T,
which
exhibits
distinct
biochemical
behaviours.
The
L20K/E73K/A82T
mutant
revertant
derived
propagating
L20K
reduced
infectivity
increased
association
polyprotein
with
membranes.
replicates
similarly
wild
type
but
retains
properties
L20K.
also
sediments
high-density
fractions
in
sucrose
gradients
after
detergent
treatment
under
conditions
fully
solubilize
WT
MA,
suggesting
enhanced
MA-MA
interactions.
Cryo-electron
tomography
subtomogram
averaging
reveals
immature
closely
resembles
type.
However,
virions
lack
detectable
lattice,
stark
contrast
both
mutant.
All-atom
molecular
dynamics
simulations
suggest
this
absence
results
from
destabilized
inter-trimer
interactions
MA.
Furthermore,
introducing
additional
mutations
designed
disrupt
does
not
impair
infectivity.
These
findings
ordered,
membrane-associated
for
providing
new
insights
plasticity
during
its
lifecycle.
Язык: Английский
Development and Optimization of Oligonucleotide Ligation Assay (OLA) Probes for Detection of HIV-1 Resistance to Dolutegravir
Viruses,
Год журнала:
2024,
Номер
16(7), С. 1162 - 1162
Опубликована: Июль 19, 2024
The
WHO
currently
recommends
dolutegravir
(DTG)-based
ART
for
persons
living
with
HIV
infection
in
resource-limited-settings
(RLS).
To
expand
access
to
testing
drug
resistance
(DR)
DTG
RLS,
we
developed
probes
use
the
oligonucleotide
ligation
assay
(OLA)-Simple,
a
near-point
of
care
DR
kit.
Genotypic
data
from
clinical
trials
and
case
reports
were
used
determine
mutations
HIV-1
integrase
critical
identifying
individuals
DTG-resistance
at
virologic
failure
DTG-based
ART.
Probes
detect
G118R,
Q148H/K/R,
N155H
R263K
subtypes
A,
B,
C,
D
CRF01_AE
designed
using
sequence
alignments
Los
Alamos
database
validated
61
samples
D,
genotyped
by
PacBio
(n
=
15)
or
Sanger
46).
Initial
OLA
failed
ligate
16/244
(6.5%)
codons
(9
G118R
7
Q148H/K/R).
revised
accommodate
polymorphisms
interfering
Q148R
reduced
indeterminates
3.7%
(5
4
Q148H/K/R)
detected
DTG-mutations
sensitivity
96.5%
100%
specificity.
These
appear
highly
sensitive
specific
across
common
RLS
high
burden
infection.
Язык: Английский