Linking the spread of CCR5-tropic HIV-1 to the eradication of

the smallpox virus

Christine Prochnow Bio113 11/5/10- Biology Department- Santa Clara University

Can
Can the
the Smallpox
Smallpox Methods:
Methods: Checked
Checked all
all subjects
subjects were
were HIV
HIV negative.
negative. Vaccinated
Vaccinated selected
selected subjects
subjects (n=9)
(n=9) with
with Drycax.
Drycax. Checked
Checked for
for
successful
successful vaccination
vaccination through
through repeated
repeated visual
visual inspections.
inspections. TheThe rest
rest ofof the
the subjects
subjects (n=10),
(n=10), were
were not
not vaccinated
vaccinated against
against
vaccine
vaccine reduce
reduce smallpox.
smallpox. All
All blood
blood samples
samples fromfrom all
all subjects
subjects were
were drawn
drawn andand were
were immediately
immediately processed
processed to to separate
separate the
the PBMCs.
PBMCs. CellCell
cultures
cultures were incubated at 37ºC in a CO incubator
were incubated at 37ºC in a CO 22
incubator forfor 22 days
days then
then either
either anan R5
R5 strain
strain (HIV-1ADA)
(HIV-1ADA) or or an
an X4
X4 strain
strain (HIV-
the
the spread
spread of
of HIV?
HIV? 1NL4-3)
1NL4-3) was
was mixed
mixed withwith an
an equal
equal volume
volume of of either
either culture
culture medium
medium or or serum
serum from
from each
each individual
individual subject
subject and
and then
then
(HIV-

incubated
incubated on
on ice
ice for
for 77 hours
hours after
after which
which 175
175 μlμl of
of each
each mixture
mixture was
was inoculated
inoculated into
into the
the appropriate
appropriate autologous
autologous cell
cell
cultures.
cultures. Measurements
Measurements of of viral
viral replication
replication were
were taken
taken byby reverse
reverse transcriptase
transcriptase assays
assays on on days
days 2,2, 5,8,10
5,8,10 and
and 13.
13.
Introduction:
Introduction:
As
As explained
explained in in Viruses,
Viruses,
Plagues
Plagues and
and History
History by
Michael
by Results:
Results: Conclusions
Conclusions
Michael B.A.
B.A. Oldstone,the
Oldstone,the
smallpox
smallpox virus
virus has
has been
been ••Significant
eradicated Significant interaction
interaction
eradicated since
since 1979.
1979. between
Because between HIV-1
HIV-1 (CCR5-
(CCR5-
Because of of its
its eradication,
eradication, the
the
smallpox tropic)
tropic) resistance
resistance and
and the
the
smallpox vaccine
vaccine is is no
no longer
longer
administered
administered except
except to to smallpox
smallpox virus
virus vaccine
vaccine due
due
scientists
scientists who
who handle
handle to
to alterations
alterations of
of CCR5.
CCR5.
remaining
remaining cultures
cultures of of smallpox
smallpox ••However,
However, not
not mediated
mediated by
by
and
and military
military personnel.
personnel.
the
the sudden
sudden release
release of
of
Today,
Today, HIVHIV is
is considered
considered to to be
be chemokines
chemokines (MIP-1α
(MIP-1α and
and
the
the current
current plague
plague and and has
has no no MIP-1β.
MIP-1β.
cure
cure oror vaccine.
vaccine. Because
Because of of its
its
unexplained
unexplained and and sudden
sudden ••Therefore,
Therefore, must
must be
be by
by
appearance
appearance throughout
throughout the the some
Figure
Figure 1.
1. Decrease
Decrease of of R5
R5 HIV-1
HIV-1 replication
replication in
in cells
cells from
from subjects
subjects vaccinated
vaccinated with
with some other
other mechanism.
mechanism.
world
world during
during the
the eradication
eradication of of
smallpox.
smallpox. Three
Three fold
fold decrease
decrease in
in vaccinated
vaccinated subjects
subjects than
than from
from unvaccinated
unvaccinated ••Future:
smallpox
smallpox andand the
the end
end of
of Future: further
further studies
studies
smallpox subjects
subjects on
on days
days 10
10 and
and 13.
13.
smallpox vacciniation,
vacciniation, aa recent
recent with
with larger
larger groups
groups should
should
experiment
experiment was was performed
performed in in be
be done
done toto see
see ifif the
the
order
order toto explore
explore ifif there
there is
is any
any smallpox
smallpox vaccine
vaccine can can be
be
relation
relation between
between smallpox
smallpox and and Figure 2. No utilized
utilized as
as protection
protection to to
the
the appearance
appearance of of
HIV statistical reduce
reduce the
the spread
spread of of
HIV (described
11
(described below).
below).
significant CCR5-tropic
CCR5-tropic HIV-1
HIV-1
HIV
HIV exploits
exploits CCR5
CCR5 as as aa co-
co- difference found specifically
specifically oror to
to use
use
receptor
receptor to to initiate
initiate infection
infection in in between high levels additionally
additionally with
with other
other anti-
anti-
CD4+
CD4+ lymphocytes
lymphocytes and and of levels of MIP-1α
mononuclear ne HIV
HIV medications;
medications; such such as
as
mononuclear cells. cells. Growing
Growing and MIP-1β in
evidence protease
protease inhibitors.
inhibitors.
evidence suggests
suggests that that many
many 60
ss
PBMC cultures of
pox
pox viruses
viruses require
require thethe References:
vaccinated and
presence
presence of of CCR5,
CCR5, and and itit is
is unvaccinated 1. Weinstein et al.,
possible
possible that
that infection
infection with
with
some
subjects. “Significantly reduced
some poxviruses
poxviruses may may alter
alter thethe 40
expression
expression of of CCR5
CCR5 on on cell
cell CCR5-tropic HIV-1
surfaces,
surfaces, which
which would
would interfere
interfere replicationinvitroincellsfrom
30
with
with HIV-1
HIV-1 infection.
infection. TheThe study,
study, Conscientious Vulnerability
Dutifulness subjectspreviouslyimmunize
in
in vitro,
vitro, compared
compared the the dwithVaccinia Virus” BMC
20
susceptibility
susceptibility of of peripheral
peripheral N O C* 1 3 1 3 5 1 3 5 1 3 5 1 3* 5
2 4 6
Immunology 2010, 11:23
E A 2 4 6* 2 4 6 2 4 6 2 4 6
blood
blood mononuclear
mononuclear cells cells
(PBMCs)
(PBMCs) by by viral
viral replication
replication
-(Figure
-(Figure not
not shown)
shown) Smallpox
Smallpox vaccination
vaccination has
has no
no affect
affect on
on viral
viral replication
replication
through
through reverse
reverse transcriptase
transcriptase of
of X4
X4 HIV-1
HIV-1
analysis.
analysis.