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

Authors :
Hraber P
Korber B
Wagh K
Giorgi EE
Bhattacharya T
Gnanakaran S
Lapedes AS
Learn GH
Kreider EF
Li Y
Shaw GM
Hahn BH
Montefiori DC
Alam SM
Bonsignori M
Moody MA
Liao HX
Gao F
Haynes BF
Source :
Viruses [Viruses] 2015 Oct 21; Vol. 7 (10), pp. 5443-75. Date of Electronic Publication: 2015 Oct 21.
Publication Year :
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.

Details

Language :
English
ISSN :
1999-4915
Volume :
7
Issue :
10
Database :
MEDLINE
Journal :
Viruses
Publication Type :
Academic Journal
Accession number :
26506369
Full Text :
https://doi.org/10.3390/v7102881