Comparative study of intra-host HIV evolution: Emergence of viral - PowerPoint PPT Presentation

>>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  Phases of HIV infection  Data Set  Diversity of Viral Sequences  Outlook http://www.spiegel.de/wissenschaft/ Federal Institute for Vaccines and Biomedicines Section 1/4 - Biostatistics

Phases of HIV infection  Clinical classification AIDS I II III Pantaleo G et al . (1993) Federal Institute for Vaccines and Biomedicines Section 1/4 - Biostatistics

Phases of HIV infection  Evolutionary classification  diversity (among strains)  divergence (from founder strain) Diversity Divergence t Early Intermediate Late CXCR4 emerge CXCR4 peak Shankarappa R et al . (1999) Federal Institute for Vaccines and Biomedicines Section 1/4 - Biostatistics

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

NRTI PI Data NNRTI other Federal Institute for Vaccines and Biomedicines Section 1/4 - Biostatistics

Diversity – Pairwise distances  RAxML (Randomized Axelerated Maximum Likelihood)  Maximum Likelihood (ML)-based inference of phylogenetic trees Stamatakis A et al . (2005) Federal Institute for Vaccines and Biomedicines 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 Drummond AJ and Rambaut A (2007) Federal Institute for Vaccines and Biomedicines Section 1/4 - Biostatistics

Skyline reconstruction Patient 004 Federal Institute for Vaccines and Biomedicines Section 1/4 - Biostatistics

Data Bayesian Skyline Diversity Federal Institute for Vaccines and Biomedicines Section 1/4 - Biostatistics

Search for evolutionary patterns  Therapy success  decrease of viral load, increase of CD4 cell count  increase of viral diversity  selection for diversity ? Patient 097 Federal Institute for Vaccines and Biomedicines Section 1/4 - Biostatistics

Search for evolutionary patterns  Therapy failure  increase of viral load, decrease of CD4 cell count  decrease of viral diversity  survival of the fastest ? Patient 005 Federal Institute for Vaccines and Biomedicines Section 1/4 - Biostatistics

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

Thank you! max planck institut informatik Klinikum und Fachbereich Medizin Johann Wolfgang Goethe-Universität Frankfurt am Main Alexander Thielen Hans-Reinhard Brodt Timo Wolf Beverley Jennings Christel Kamp Barbara Schnierle Christian Schneider Dorothea Binninger-Schinzel Benjamin Kraus Birgit Krause Kay Hamacher Britta Neumann Gudrun Winskowsky Federal Institute for Vaccines and Biomedicines Section 1/4 - Biostatistics

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