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Natural Scrub Typhus Antibody Suppresses HIV CXCR4(X4) Viruses.
[scrub typhus]
Viral
load
generally
rises
in
HIV-infected
individuals
with
a
concomitant
infection
,
but
falls
markedly
in
some
individuals
with
scrub
typhus
(
ST
)
,
a
common
Asian
rickettsial
infection
.
ST
infection
appears
to
shift
the
viral
population
from
CXCR
4
-
using
(
X
4
)
to
CCR
5
-
utilizing
(
R
5
)
strains
,
and
there
is
evidence
of
cross-reactivity
between
ST-
specific
antibodies
and
HIV-
1
.
We
examined
the
mechanism
of
ST
suppression
of
HIV
by
measuring
the
effects
of
ST
infection
on
X
4
and
R
5
viruses
in
vivo
and
in
vitro
,
and
assessing
the
relative
contributions
of
antibodies
and
chemokines
to
the
inhibitory
effect
.
In
vivo
,
a
single
scrub
typhus
plasma
infusion
markedly
reduced
the
subpopulation
of
HIV-
1
viruses
using
the
X
4
co
-receptor
in
all
8
recipients
,
and
eliminated
X
4
viruses
6
patients
.
In
vitro
,
the
14
ST
sera
tested
all
inhibited
the
replication
of
an
X
4
but
not
an
R
5
virus
.
This
inhibitory
effect
was
maintained
if
ST
sera
were
depleted
of
chemokines
but
was
lost
upon
removal
of
antibodies
.
Sera
from
STinfected
mice
recognized
a
target
that
co
-
localized
with
X
4
HIV
gp
120
in
immunofluorescent
experiments
.
These
in
vivo
and
in
vitro
data
suggest
that
acute
ST
infection
generates
cross-reactive
antibodies
that
produce
potent
suppression
of
CXCR
4
-
but
not
CCR
5
-
using
HIV-
1
viruses
.
ST
suppression
of
HIV
replication
could
reveal
novel
mechanisms
that
could
be
exploited
for
vaccination
strategies
,
as
well
as
aid
in
the
development
of
fusion
inhibitors
and
other
new
therapeutic
regimens
.
This
also
appears
to
be
the
first
instance
where
one
pathogen
is
neutralized
by
antibody
produced
in
response
to
infection
by
a
completely
unrelated
organism
.