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Viruses 2015, 7(10), 5443-5475; doi:10.3390/v7102881

Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants

1
Los Alamos National Laboratory, Los Alamos, NM 87545, USA
2
Santa Fe Institute, Santa Fe, NM 87501, USA
3
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
4
Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Viktor Müller
Received: 31 July 2015 / Revised: 1 October 2015 / Accepted: 5 October 2015 / Published: 21 October 2015
(This article belongs to the Special Issue Bioinformatics and Computational Biology of Viruses)
View Full-Text   |   Download PDF [2881 KB, uploaded 21 October 2015]   |  

Abstract

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. View Full-Text
Keywords: human immunodeficiency virus type 1; vaccine; neutralizing antibodies; immunogen design; envelope glycoprotein; coevolution; immune escape; quasispecies; antigenic swarm; selection human immunodeficiency virus type 1; vaccine; neutralizing antibodies; immunogen design; envelope glycoprotein; coevolution; immune escape; quasispecies; antigenic swarm; selection
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Hraber, P.; Korber, B.; Wagh, K.; Giorgi, E.E.; Bhattacharya, T.; Gnanakaran, S.; Lapedes, A.S.; Learn, G.H.; Kreider, E.F.; Li, Y.; Shaw, G.M.; Hahn, B.H.; Montefiori, D.C.; Alam, S.M.; Bonsignori, M.; Moody, M.A.; Liao, H.-X.; Gao, F.; Haynes, B.F. Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants. Viruses 2015, 7, 5443-5475.

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