Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants
| Autor: | Yingying Li, Mattia Bonsignori, M. A. Moody, Bette T. Korber, Peter T. Hraber, Feng Gao, Gerald H. Learn, S.M. Alam, Barton F. Haynes, Alan Lapedes, Beatrice H. Hahn, Kshitij Wagh, George M. Shaw, Hua-Xin Liao, Sandrasegaram Gnanakaran, Edward F. Kreider, Elena E. Giorgi, Tanmoy Bhattacharya, David C. Montefiori |
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| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
immunogen design
lcsh:QR1-502 envelope glycoprotein selection HIV Infections Viral quasispecies Biology Quantitative Biology - Quantitative Methods lcsh:Microbiology DNA sequencing Epitope Virus Article human immunodeficiency virus type 1 Antigen Virology vaccine Genetic variation neutralizing antibodies coevolution immune escape quasispecies antigenic swarm Humans Longitudinal Studies Selection Genetic Quantitative Biology - Populations and Evolution Antigens Viral Quantitative Methods (q-bio.QM) Immune Evasion Genetics Phylogenetic tree Populations and Evolution (q-bio.PE) Genetic Variation HIV 3. Good health Infectious Diseases FOS: Biological sciences biology.protein Antibody |
| Zdroj: | Viruses; Volume 7; Issue 10; Pages: 5443-5475 Viruses Viruses, Vol 7, Iss 10, Pp 5443-5475 (2015) Volume 7 Issue 10 Pages 5443-5475 |
| ISSN: | 1999-4915 |
| DOI: | 10.3390/v7102881 |
| Popis: | Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that generate within-subject epitope diversity. Comprehensive identification of immune-escape mutations is experimentally and computationally challenging. With current technology, many more viral sequences can readily be obtained than can be tested for binding and neutralization, making down-selection necessary. Typically, this is done manually, by picking variants that represent different time-points and branches on a phylogenetic tree. Such strategies are likely to miss many relevant mutations and combinations of mutations, and to be redundant for other mutations. Longitudinal Antigenic Sequences and Sites from Intrahost Evolution (LASSIE) uses transmitted-founder loss to identify virus "hot-spots" under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. LASSIE favors earliest sequences in which mutations arise. With well-characterized longitudinal Env sequences, we confirmed selected sites were concentrated in antibody contacts and selected sequences represented diverse antigenic phenotypes. Practical applications include rapidly identifying immune targets under selective pressure within a subject, selecting minimal sets of reagents for immunological assays that characterize evolving antibody responses, and for immunogens in polyvalent "cocktail" vaccines. 73 pages, 10 figures, 8 supplemental figures; 18 full-resolution figures appear at the end of the manuscript. Presented at 22nd International Workshop on HIV Dynamics and Evolution, Budapest, May 2015 |
| Databáze: | OpenAIRE |
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