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microbial translocation
during hyperacute SIV
infection
Adam Ericsen1,2, Michael Lauck3, Mariel Mohns3, Sarah DiNapoli4, James
Mutschler5, Justin Greene3, Jason Weinfurter1, Gabrielle Lehrer-Brey5, Kristin
Crosno5, Eric Peterson5, Matthew Reynolds1, Roger Wiseman1, Benjamin Burwitz6,7,
Jonah Sacha6,7, Thomas Friedrich 5,8, Jason Brenchley4, David O'Connor 1,5
1 University of Wisconsin-Madison, Pathology and Laboratory Medicine, Madison, United States, 2 University of Wisconsin-Madison, Virology
Training Program, Madison, United States, 3 University of Wisconsin-Madison, Madison, United States, 4 National Institute of Allergy and
Infectious Disease, Laboratory of Molecular Microbiology, Bethesda, United States, 5 Wisconsin National Primate Research Center, Madison,
United States, 6 Oregon Health & Sciences University, Vaccine & Gene Therapy Institute, Beaverton, United States, 7 Oregon Health &
Sciences University, National Primate Research Center, Beaverton, United States, 8 University of Wisconsin-Madison, Pathobiological
Sciences, Madison, United States
viremia drives disease
progression
SIV RNA copies/ml
9
8
hypothesis
7
6
the composition of the gut or blood
microbial community differentiates
controllers from progressors.
5
4
3
2
0
7
14
21
28
35
42
days post-infection
[y-axis is log 10-transformed]
49
56
63
70
77
84
91
98 105 112 119 126 133 140
but what drives viremia?
SIV RNA copies/ml
9
hypothesis
8
7
the composition of the gut or blood
microbial communities differentiates
controllers from progressors.
6
5
4
3
2
0
7
14
21
28
35
42
days post-infection
[y-axis is log 10-transformed]
49
56
63
70
77
84
91
98 105 112 119 126 133 140
study design
intrarectal
SIVmac239
-42
0
8
14 18 21 35 56
monitored into
chronic infection
days post-infection
‣ 8 macaques
‣ MHC-identical
(HLA-A & HLA-B)
16S rDNA seq of stool
16S rDNA seq & qPCR of plasma
flow cytometry PBMC (CD4+CCR5+)
plasma analyte ELISA
cynomolgus macaques
rhesus macaques
16S rDNA copies/ml
6
5
4
3
2
1
-5
0
5
10
15
20
Day Post-Infection
days post SIV infection
25
30
35
LPS-binding antibodies (EndoCAb)
soluble CD14
frequency
absolute count
but does microbial translocation increase viremia?
inducing microbial translocation
in macaque elite controllers
water with 0.5% dextran
sulfate sodium (DSS)
administered orally
intrarectal
SIVmac239
+1 year
-35 -21 -14
-7
0
1
2
3
4
…
days post-DSS
treatment
days post-dextran
sulfate
sodium
(DSS) treatment
monitored for
10 weeks
inducing microbial translocation
in macaque elite controllers
Data 2
Data 2
simian immunodeficiency
virus
infection
water with
0.5%
dextran
7
sulfate sodium (DSS)
administered orally
6 intrarectal
SIVmac239
5
4
monitored for
8 weeks
+1 year
3
-35 -21 -14
1
2
3
4
…
days post-infection
days post-DSS
0DSS
330
325
340
-5
320
335
80 120 160 200 240 280 -20 -15 -10
315
330
310
325
305
320
300
315
280
310
240
305
300
200
280
160
240
120
40
200
80
0
160
40
120
0
80
0
days post-DSS treatment
2
40
-7
DSS
6
water with 0.5% dextran
sulfate sodium (DSS)
administered orally
intrarectal
5 SIVmac239
4
+1 year
3
-35 -21 -14
-7
0
1
2
3
4
…
monitored for
8 weeks
Dayssulfate
Post-DSS
days post-dextran
sodium treatment
70
65
60
55
50
45
40
35
30
25
20
15
10
5
0
-5
-10
-15
-20
-25
2
-30
days post-DSS treatment
-35
Log10 vRNA copies/ml plasma
inducing microbial translocation
in macaque elite controllers
inducing microbial translocation
in macaque elite controllers
increased plasma levels of
intestinal fatty-acid binding protein
increased plasma
water with 0.5%16S
dextran
rDNA load
sulfate sodium (DSS)
administered orally
intrarectal
SIVmac239
+1 year
-35 -21 -14
-7
0
1
2
3
4
…
days post-DSS treatment
days post-dextran sulfate sodium treatment
monitored for
8 weeks
inducing microbial translocation
in macaque elite controllers
water with 0.5% dextran
sulfate sodium (DSS)
administered orally
intrarectal
SIVmac239
+1 year
-35 -21 -14
-7
0
1
2
3
4
…
days post-DSS treatment
days post-dextran sulfate sodium treatment
monitored for
8 weeks
acknowledgements
‣ AIDS Vaccine Research Laboratory
•
•
•
•
•
•
•
Meghan Breitbach
Ken Drinkwater
Dawn Dudley
Thomas Friedrich
Samantha Gieger
Michael Graham
Justin Greene
•
•
•
•
•
•
•
Julie Karl
Michael Lauck
Gabrielle Lehrer-Brey
Mariel Mohns
James Mutschler
David O’Connor
Trent Prall
‣ Wisconsin National Primate
Research Center
• Kristin Crosno
• Eric Peterson
• Buddy Capuano
‣ NIAID
• Sarah DiNapoli
• Jason Brenchley
•
•
•
•
•
Eva Rakesz
Mustafa Rasheed
Matthew Reynolds
Jason Weinfurter
Roger Wiseman
‣ Oregon Health &
Sciences University
• Benjamin Burwitz
• Jonah Sacha
‣ NCI
• Jacob Estes
‣ Funding
• NIH
• T32 AI078985