semen -...
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![Page 1: SEMEN - regist2.virology-education.comregist2.virology-education.com/2011/6Hivtrans/docs/04_Introini.pdfSEMEN • Is a complex fluid that contains spermatozoa and soluble factors,](https://reader031.vdocuments.mx/reader031/viewer/2022011809/5ccf7d7588c993cc718bd5a3/html5/thumbnails/1.jpg)
Presented at the 6th Int. Workshop on HIV Transmission, 14 – 15 July 2011, Rome, Italy
HIV-1 and Reactivated Coinfecting Herpesviruses Rearrange the Cytokine Network in Semen
of Infected Individuals
Andrea Introini,
National Institute of Child Health and Human Development
NIH
Bethesda, MD, U.S.A.
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Presented at the 6th Int. Workshop on HIV Transmission, 14 – 15 July 2011, Rome, Italy
SEMEN
• Is a complex fluid that contains spermatozoa and
soluble factors, including cytokines
• Natural carrier of many pathogens
• Pathogens replication is affected by cytokines and
also affect cytokine expression
Do HIV-1 infection and coinfecting herpesviruses
affect cytokine profile in semen?
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Presented at the 6th Int. Workshop on HIV Transmission, 14 – 15 July 2011, Rome, Italy
OUR STUDY
• Viral load of:
HIV-1
Herpes Simplex Virus-2 (HHV-2)
Epstein Barr Virus (HHV-4)
Cytomegalovirus (HHV-5)
HHV-6 A and B
HHV-7
HHV-8
Blood and seminal plasma from:
• 74 HIV-1-infected individuals therapy naïve
• 33 uninfected individuals
• Cytokines
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Presented at the 6th Int. Workshop on HIV Transmission, 14 – 15 July 2011, Rome, Italy
HIV-1 LOAD L
og
10 (
co
pie
s/m
l)
Blood Semen
100%
positive
94%
positive
HIV-1 blood load Log10 (copies/ml)
HIV
-1 s
em
en load
Log
10 (
co
pie
s/m
l)
R=0.64 p<0.0001
4.5 4.0
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Presented at the 6th Int. Workshop on HIV Transmission, 14 – 15 July 2011, Rome, Italy
0
20
40
60
80
HERPESVIRUSES REACTIVATION
p<0.001
HIV-1-infected HIV-1-uninfected
Semen
Blood
po
sitiv
e s
am
ple
s (
%)
CMV ML vs log10(copies/ml)
* *
positiv
e s
am
ple
s (
%)
EBV ML vs log10(copies/ml)
0
5
10
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Presented at the 6th Int. Workshop on HIV Transmission, 14 – 15 July 2011, Rome, Italy
1
2
3
4
5
6
7
8
9
CMV
Vira
l lo
ad
Log
10
(copie
s/m
l)
Blood Semen
HIV-1-CMV coinfected
77% semen only
19% both semen and blood
3% blood only
CMV REACTIVATION IS COMPARTMENTALIZED
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Presented at the 6th Int. Workshop on HIV Transmission, 14 – 15 July 2011, Rome, Italy
CONCURRENT EBV AND CMV INFECTION IS ASSOCIATED WITH AN
HIGHER HIV-1 SHEDDING IN SEMEN
p<0.05 V
ira
l lo
ad
Log
10 (
copie
s/m
l)
HIV-1 *
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Presented at the 6th Int. Workshop on HIV Transmission, 14 – 15 July 2011, Rome, Italy
CYTOKINE PANEL
• Pro-inflammatory cytokines: IL-1α, IL-1β, IL-6,
IFN-γ, TNF-α
• Anti-inflammatory cytokines: TGF-β
• CCR5 ligands: RANTES, MIP-1α, MIP-1β, Eotaxin
• CXCR4 ligands: SDF-1β
• Chemokines: MCP-1, MIP-3α, IP-10, MIG, IL-8
• Growth factors: IL-2, IL-7, IL-15, IL-16, GM-CSF
![Page 9: SEMEN - regist2.virology-education.comregist2.virology-education.com/2011/6Hivtrans/docs/04_Introini.pdfSEMEN • Is a complex fluid that contains spermatozoa and soluble factors,](https://reader031.vdocuments.mx/reader031/viewer/2022011809/5ccf7d7588c993cc718bd5a3/html5/thumbnails/9.jpg)
Presented at the 6th Int. Workshop on HIV Transmission, 14 – 15 July 2011, Rome, Italy
SEMEN AND BLOOD ARE SEPARATE IMMUNE COMPARTMENTS (UNINFECTED MEN)
Semen/Blood MEDIAN RATIO
Enriched
in semen
Enriched
in blood
*
* *
* *
* * *
*
*
* *
*
= p<0.05 *
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Presented at the 6th Int. Workshop on HIV Transmission, 14 – 15 July 2011, Rome, Italy
HIV-1 UPREGULATES FEW CYTOKINES IN BLOOD
N-f
old
0
2
4
6
8
HIV-1+/HIV-1- RATIO
0.1
= p<0.05
1
* * *
* *
*
*
*
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Presented at the 6th Int. Workshop on HIV Transmission, 14 – 15 July 2011, Rome, Italy
1
3
5
7
N-f
old
= p<0.05
HIV-1 UPREGULATES MANY CYTOKINES IN SEMEN
HIV-1+/HIV-1- RATIO
* *
*
*
* * *
*
*
*
* * * *
*
*
*
![Page 12: SEMEN - regist2.virology-education.comregist2.virology-education.com/2011/6Hivtrans/docs/04_Introini.pdfSEMEN • Is a complex fluid that contains spermatozoa and soluble factors,](https://reader031.vdocuments.mx/reader031/viewer/2022011809/5ccf7d7588c993cc718bd5a3/html5/thumbnails/12.jpg)
Presented at the 6th Int. Workshop on HIV Transmission, 14 – 15 July 2011, Rome, Italy
HIV-1 INFECTION REARRANGES THE CYTOKINE NETWORK IN SEMEN
HIV-1-infected
HIV-1-noninfected
Spearman’s rank
correlation coefficient
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Presented at the 6th Int. Workshop on HIV Transmission, 14 – 15 July 2011, Rome, Italy
CONCLUSIONS
• EBV and CMV reactivate in the course of HIV-1 infection
predominantly in semen
• HIV-1 infection increases the number and the strength of
correlations between cytokines in semen
• Concurrent shedding of CMV and EBV in semen is
associated with higher HIV-1 seminal load
• HIV-1 infection upregulates more cytokines in semen than
in blood
• Blood and semen are two separate immunological
compartments with different cytokine profiles
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Presented at the 6th Int. Workshop on HIV Transmission, 14 – 15 July 2011, Rome, Italy
CONCLUSION
HIV-1 together with its copathogens significantly change the
immunological landscape of semen, probably affecting HIV-1
evolution in this compartment and selecting for transmissible
HIV-1 variants.
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Presented at the 6th Int. Workshop on HIV Transmission, 14 – 15 July 2011, Rome, Italy
Leonid Margolis
Andrea Lisco
Christophe Vanpouille
Jean-Charles Grivel
Wendy Fitzgerald
Anush Arakelyan
Sarman Singh
Arshi Munawwar