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Within-host whole-genome deep sequencing and diversity analysis of human respiratory syncytial virus infection reveals dynamics of genomic diversity in the absence and presence of immune pressure.
[severe combined immunodeficiency]
Human
respiratory
syncytial
virus
(
RSV
)
is
the
leading
cause
of
lower
respiratory
tract
disease
in
infants
and
young
children
and
an
important
respiratory
pathogen
in
the
elderly
and
immunocompromised
.
While
population-
wide
molecular
epidemiology
studies
have
shown
multiple
cocirculating
RSV
genotypes
and
revealed
antigenic
and
genetic
change
over
successive
seasons
,
little
is
known
about
the
extent
of
viral
diversity
over
the
course
of
an
individual
infection
,
the
origins
of
novel
variants
,
or
the
effect
of
immune
pressure
on
viral
diversity
and
potential
immune-escape
mutations
.
To
investigate
viral
population
diversity
in
the
presence
and
absence
of
selective
immune
pressures
,
we
studied
whole-genome
deep
sequencing
of
RSV
in
upper
airway
samples
from
an
infant
with
severe
combined
immune
deficiency
syndrome
and
persistent
RSV
infection
.
The
infection
continued
over
several
months
before
and
after
bone
marrow
transplant
(
BMT
)
from
his
RSV-immune
father
.
RSV
diversity
was
characterized
in
26
samples
obtained
over
78
days
.
Diversity
increased
after
engraftment
,
as
defined
by
T
-
cell
presence
,
and
populations
reflected
variation
mostly
within
the
G
protein
,
the
major
surface
antigen
.
Minority
populations
with
known
palivizumab
resistance
mutations
emerged
after
its
administration
.
The
viral
population
appeared
to
diversify
in
response
to
selective
pressures
,
showing
a
statistically
significant
growth
in
diversity
in
the
presence
of
pressure
from
immunity
.
Defining
escape
mutations
and
their
dynamics
will
be
useful
in
the
design
and
application
of
novel
therapeutics
and
vaccines
.
These
data
can
contribute
to
future
studies
of
the
relationship
between
within-host
and
population-
wide
RSV
phylodynamics
.
Human
RSV
is
an
important
cause
of
respiratory
disease
in
infants
,
the
elderly
,
and
the
immunocompromised
.
RSV
circulating
in
a
community
appears
to
change
season
by
season
,
but
the
amount
of
diversity
generated
during
an
individual
infection
and
the
impact
of
immunity
on
this
viral
diversity
has
been
unclear
.
To
address
this
question
,
we
described
within-host
RSV
diversity
by
whole-genome
deep
sequencing
in
a
unique
clinical
case
of
an
RSV-infected
infant
with
severe
combined
immunodeficiency
and
effectively
no
adaptive
immunity
who
then
gained
adaptive
immunity
after
undergoing
bone
marrow
transplantation
.
We
found
that
viral
diversity
increased
in
the
presence
of
adaptive
immunity
and
was
primarily
within
the
G
protein
,
the
major
surface
antigen
.
These
data
will
be
useful
in
designing
RSV
treatments
and
vaccines
and
to
help
understand
the
relationship
between
the
dynamics
of
viral
diversification
within
individual
hosts
and
the
viral
populations
circulating
in
a
community
.
Diseases
Validation
Diseases presenting
"bone marrow transplant"
symptom
dystrophic epidermolysis bullosa
krabbe disease
monosomy 21
oculocutaneous albinism
omenn syndrome
severe combined immunodeficiency
x-linked adrenoleukodystrophy
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