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>>www.pei.de Comparative study of intra-host HIV evolution: Emergence of viral diversity Miriam Carbon-Mangels, Barbara Schnierle, Christel Kamp AREVIR 2011 Federal Institute for Vaccines and Biomedicines Outline of the Presentation

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>>www.pei.de

Federal Institute for Vaccines and Biomedicines

Comparative study of intra-host HIV evolution: Emergence of viral diversity

Miriam Carbon-Mangels, Barbara Schnierle, Christel Kamp AREVIR 2011

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Section 1/4 - Biostatistics Federal Institute for Vaccines and Biomedicines

Outline of the Presentation

  • Phases of HIV infection
  • Data Set
  • Diversity of Viral Sequences
  • Outlook

http://www.spiegel.de/wissenschaft/

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Section 1/4 - Biostatistics Federal Institute for Vaccines and Biomedicines

Phases of HIV infection

  • Clinical classification

I II III

AIDS

Pantaleo G et al. (1993)

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Section 1/4 - Biostatistics Federal Institute for Vaccines and Biomedicines

Phases of HIV infection

  • Evolutionary classification
  • diversity (among strains)
  • divergence (from founder strain)

Diversity Divergence Early Intermediate Late CXCR4 emerge CXCR4 peak t

Shankarappa R et al. (1999)

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Section 1/4 - Biostatistics Federal Institute for Vaccines and Biomedicines

Data

  • Sequences of the V3 loop
  • 2.215 sequences of 214 visits (avg. ~60 seq. in 6 visits)
  • 37 patients: 35 male, 2 female
  • Exceptional availability of an integrated dataset
  • clinical data
  • date of first HIV-positive test
  • viral load
  • CD4 cell count
  • co-infections
  • information on therapy
  • risk
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Section 1/4 - Biostatistics

Data

Federal Institute for Vaccines and Biomedicines PI

  • ther

NRTI NNRTI

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Section 1/4 - Biostatistics Stamatakis A et al. (2005)

Diversity – Pairwise distances

Federal Institute for Vaccines and Biomedicines

  • RAxML (Randomized Axelerated Maximum Likelihood)
  • Maximum Likelihood (ML)-based inference of phylogenetic

trees

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Section 1/4 - Biostatistics

Diversity – Bayesian skyline plot

  • BEAST (Bayesian Evolutionary Analysis by Sampling

Trees)

  • creates a phylogeny which lineages coalesce towards the

most recent common ancestor (MRCA)

  • Bayesian skyline plot
  • method to estimate the effective population size through

time from reconstructed phylogenetic tree

Federal Institute for Vaccines and Biomedicines Drummond AJ and Rambaut A (2007)

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Section 1/4 - Biostatistics

Skyline reconstruction

Federal Institute for Vaccines and Biomedicines

Patient 004

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Section 1/4 - Biostatistics

Data

Federal Institute for Vaccines and Biomedicines Bayesian Skyline Diversity

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Section 1/4 - Biostatistics

  • Therapy success
  • decrease of viral load, increase of CD4 cell count
  • increase of viral diversity
  • selection for diversity ?

Search for evolutionary patterns

Federal Institute for Vaccines and Biomedicines

Patient 097

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Section 1/4 - Biostatistics

  • Therapy failure
  • increase of viral load, decrease of CD4 cell count
  • decrease of viral diversity
  • survival of the fastest ?

Search for evolutionary patterns

Federal Institute for Vaccines and Biomedicines

Patient 005

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Section 1/4 - Biostatistics Federal Institute for Vaccines and Biomedicines

Outlook

  • HIV evolution is primarily shaped through the

interaction with its dynamic environment

  • hosts’ immune response
  • antiretroviral therapy
  • co-infections
  • diversity and divergence

Shankarappa R et al. (1999)

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Section 1/4 - Biostatistics Federal Institute for Vaccines and Biomedicines

Thank you!

Klinikum und Fachbereich Medizin Johann Wolfgang Goethe-Universität Frankfurt am Main

Hans-Reinhard Brodt Timo Wolf Beverley Jennings Christel Kamp Barbara Schnierle Christian Schneider Dorothea Binninger-Schinzel Benjamin Kraus Birgit Krause Britta Neumann Gudrun Winskowsky Kay Hamacher

max planck institut informatik

Alexander Thielen

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Section 1/4 - Biostatistics Federal Institute for Vaccines and Biomedicines

References

  • New concepts in the immunopathogenesis of human immunodeficiency virus infection,

Pantaleo G et al., New England Journal of Medicine, 1993, 328 (5)

  • Consistent Viral Evolutionary Changes Associated with the Progression of Human

Immunodeficiency Virus Type 1 Infection, Shankarappa R et al., Virology Journal, 1999, 73(12):10489-10502

  • Raxml-iii: A fast program for maximum likelihood-based inference of large phylogenetic

trees, Stamatakis A, Ludwig T, and Meier H, Bioinformatics, 2005, 21(4), 456-463

  • "BEAST: Bayesian evolutionary analysis by sampling trees.“, Drummond AJ and

Rambaut A, BMC Evolutionary Biology, 2007, 7, 214

  • Additional image sources
  • 1: http://www.spiegel.de/wissenschaft/mensch/0,1518,grossbild-11960-

344361,00.html

  • 2: MaxPlanck Forschung 3/2005