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Paul-Ehrlich-Institut
Bundesamt für Sera und Impfstoffe
Paul-Ehrlich-Institut Barbara Schnierle - Christel Kamp
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Paul-Ehrlich-Institut
Bundesamt für Sera und Impfstoffe
Paul-Ehrlich-Institut Barbara Schnierle - Christel Kamp
Analysis of HIV evolution in a stem cell transplanted HIV patient: - - PowerPoint PPT Presentation
Analysis of HIV evolution in a stem cell transplanted HIV patient: - - PowerPoint PPT Presentation
Paul-Ehrlich-Institut Bundesamt fr Sera und Impfstoffe Analysis of HIV evolution in a stem cell transplanted HIV patient: indications for in silico modelling AREVIR-GenaFor-Meeting 24.04.2009 Paul-Ehrlich-Institut Barbara Schnierle - Christel
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SLIDE 3
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Paul-Ehrlich-Institut
Bundesamt für Sera und Impfstoffe
Paul-Ehrlich-Institut Barbara Schnierle - Christel Kamp
Our data basis
Numbers Comments Patients (total) 291 co-information on viral load, CD4 counts, therapy, co-infections… Samples 801 133 x 1 sample per patient 86 x 2-3 samples per patient 75 x 4-13 samples per patient Virus isolations 576 (86 % pos.) C2V5 sequences 2581 of 256 samples Protease sequences 1013 of 114 samples Western blot 477 all positive CCR5-Genotype 278 of 294 CCR+/CCR+: 238 CCR+/CCR-: 40 16x no DNA
Comprehensive longitudinal patient data
SLIDE 4
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Paul-Ehrlich-Institut
Bundesamt für Sera und Impfstoffe
Paul-Ehrlich-Institut Barbara Schnierle - Christel Kamp
Our data basis Comprehensive longitudinal patient data allow for → an assessment of the evolutionary dynamics of HIV infections of patients with distinct characteristics (case studies) → an assessment of evolutionary patterns of HIV infections (in general, in specific subpopulations/conditions etc.) → Goal: Refining data to information and predictive models!
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∑ ∫ ?!
SLIDE 5
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Paul-Ehrlich-Institut
Bundesamt für Sera und Impfstoffe
Paul-Ehrlich-Institut Barbara Schnierle - Christel Kamp
Our data basis Comprehensive longitudinal patient data allow for → an assessment of the evolutionary dynamics of HIV infections of patients with distinct characteristics: a stem cell transplanted patient → an assessment of evolutionary patterns of HIV infections (in general, in specific subpopulations/conditions etc.) → Goal: Refining data to information and predictive models!
…TTTACACAACAGGACAAA…
∑ ∫ ?!
SLIDE 6
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Paul-Ehrlich-Institut
Bundesamt für Sera und Impfstoffe
Paul-Ehrlich-Institut Barbara Schnierle - Christel Kamp
HIV and stem cell transplantation Learn about HIV from exceptional circumstances… Importance of target cells? Interactions between HIV and immune system? How is HIV affected by a “reset”
- f
the immune system?
SLIDE 7
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Paul-Ehrlich-Institut
Bundesamt für Sera und Impfstoffe
Paul-Ehrlich-Institut Barbara Schnierle - Christel Kamp
HIV and stem cell transplantation Learn about HIV from exceptional circumstances…another SCT patient
SCT
- Nov. 2nd, 2005
Therapy Therapy HIV specific antibodies
SLIDE 8
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Paul-Ehrlich-Institut
Bundesamt für Sera und Impfstoffe
Paul-Ehrlich-Institut Barbara Schnierle - Christel Kamp
HIV and stem cell transplantation SCT patient non-transplanted patient Virus diversity is large diminished after SCT!
Therapy Therapy
SCT
SLIDE 9
9/12
Paul-Ehrlich-Institut
Bundesamt für Sera und Impfstoffe
Paul-Ehrlich-Institut Barbara Schnierle - Christel Kamp
Our data basis Comprehensive longitudinal patient data allow for → an assessment of the evolutionary dynamics of HIV infections of patients with distinct characteristics: a stem cell transplanted patient → an assessment of evolutionary patterns of HIV infections (in general, in specific subpopulations/conditions etc.) → Goal: Refining data to information and predictive models!
…TTTACACAACAGGACAAA…
∑ ∫ ?!
SLIDE 10
10/12
Paul-Ehrlich-Institut
Bundesamt für Sera und Impfstoffe
Paul-Ehrlich-Institut Barbara Schnierle - Christel Kamp
Phenotype testing vs. in silico prediction Goal: Refining data to information and predictive models!
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∑ ∫ ?!
* * * *
PBMC or T cell line IsnoR5
CXCR4 CXCR4 CCR5
* *
*
AMD3100 AMD3100
geno2pheno PSSM
* *
SLIDE 11
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Paul-Ehrlich-Institut
Bundesamt für Sera und Impfstoffe
Paul-Ehrlich-Institut Barbara Schnierle - Christel Kamp
Phenotype testing vs. in silico prediction Validation and training of in silico models!
Samples from SCT patient Phenotype testing in silico prediction IsnoR5 (X4) PBMC (R5/X4) PBMC+AMD3100 (R5) PSSM (score ~0,94) Geno2pheno
- Nr. 786
- +
+ X4 X4
- Nr. 801
- R5
X4
- Nr. 806
- +
+ X4 X4
- Nr. 845
- +
+ X4 X4
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12/12
Paul-Ehrlich-Institut
Bundesamt für Sera und Impfstoffe
Paul-Ehrlich-Institut Barbara Schnierle - Christel Kamp
Thank you… PEI: Birgit Krause Albrecht Werner Britta Meyé Dorothea Binninger-Schinzel Gudrun Winskowsky Daniela Müller Uni-Klinikum Frankfurt: Reinhard Brodt Timo Wolf Universität Köln: Rolf Kaiser CSISP/Advanced Centre for Research in Public Health: Ignacio González Bravo
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Paul-Ehrlich-Institut
Bundesamt für Sera und Impfstoffe
Paul-Ehrlich-Institut Barbara Schnierle - Christel Kamp
HIV and stem cell transplantation
+ 18 + 20 + 27 + 34
- 9
p24 gp160 HIV-2 gp41
Serum control
gp120 p17 p66
- 10
- 61
- 92
+ 35 + 43 + 91 + 105 + 119 + 180 + 384
positive control negative control Weak reaction
days relative to transplantation
Humoral immune response to HIV-1
SLIDE 14
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Paul-Ehrlich-Institut
Bundesamt für Sera und Impfstoffe
Paul-Ehrlich-Institut Barbara Schnierle - Christel Kamp
Phenotype testing vs. in silico prediction Validation and training
- f in silico models!
Samples from SCT patient Phenotype testing in silico prediction IsnoR5 (X4) PBMC (R5/X4) PBMC+AMD3100 (R5) PSSM (score ~0,94) Geno2pheno
- Nr. 786
- +
+ X4 X4
- Nr. 801
- R5
X4
- Nr. 806
- +
+ X4 X4
- Nr. 810
- X4
X4
- Nr. 812
- X4
X4
- Nr. 815
- X4
X4
- Nr. 818
- X4
X4
- Nr. 845
- +
+ X4 X4
- Nr. 886
- X4