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Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants
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. Compre...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632389/ https://www.ncbi.nlm.nih.gov/pubmed/26506369 http://dx.doi.org/10.3390/v7102881 |
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author | Hraber, Peter Korber, Bette Wagh, Kshitij Giorgi, Elena E. Bhattacharya, Tanmoy Gnanakaran, S. Lapedes, Alan S. Learn, Gerald H. Kreider, Edward F. Li, Yingying Shaw, George M. Hahn, Beatrice H. Montefiori, David C. Alam, S. Munir Bonsignori, Mattia Moody, M. Anthony Liao, Hua-Xin Gao, Feng Haynes, Barton F. |
author_facet | Hraber, Peter Korber, Bette Wagh, Kshitij Giorgi, Elena E. Bhattacharya, Tanmoy Gnanakaran, S. Lapedes, Alan S. Learn, Gerald H. Kreider, Edward F. Li, Yingying Shaw, George M. Hahn, Beatrice H. Montefiori, David C. Alam, S. Munir Bonsignori, Mattia Moody, M. Anthony Liao, Hua-Xin Gao, Feng Haynes, Barton F. |
author_sort | Hraber, Peter |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4632389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-46323892015-11-23 Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants Hraber, Peter Korber, Bette Wagh, Kshitij Giorgi, Elena E. Bhattacharya, Tanmoy Gnanakaran, S. Lapedes, Alan S. Learn, Gerald H. Kreider, Edward F. Li, Yingying Shaw, George M. Hahn, Beatrice H. Montefiori, David C. Alam, S. Munir Bonsignori, Mattia Moody, M. Anthony Liao, Hua-Xin Gao, Feng Haynes, Barton F. Viruses Article 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. MDPI 2015-10-21 /pmc/articles/PMC4632389/ /pubmed/26506369 http://dx.doi.org/10.3390/v7102881 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Hraber, Peter Korber, Bette Wagh, Kshitij Giorgi, Elena E. Bhattacharya, Tanmoy Gnanakaran, S. Lapedes, Alan S. Learn, Gerald H. Kreider, Edward F. Li, Yingying Shaw, George M. Hahn, Beatrice H. Montefiori, David C. Alam, S. Munir Bonsignori, Mattia Moody, M. Anthony Liao, Hua-Xin Gao, Feng Haynes, Barton F. Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants |
title | Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants |
title_full | Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants |
title_fullStr | Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants |
title_full_unstemmed | Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants |
title_short | Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants |
title_sort | longitudinal antigenic sequences and sites from intra-host evolution (lassie) identifies immune-selected hiv variants |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632389/ https://www.ncbi.nlm.nih.gov/pubmed/26506369 http://dx.doi.org/10.3390/v7102881 |
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