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

Viruses

Barton F. Haynes¹  David C. Montefiori¹  Hua-Xin Liao¹  S. Munir Alam¹  M. Anthony Moody¹  Mattia Bonsignori¹  Feng Gao¹  Bette Korber²  Peter Hraber²  Elena E. Giorgi²  Tanmoy Bhattacharya²  Kshitij Wagh²  Alan S. Lapedes²  S. Gnanakaran²  George M. Shaw³  Beatrice H. Hahn³  Gerald H. Learn³  Edward F. Kreider³  Yingying Li³ 

[1] Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA;Los Alamos National Laboratory, Los Alamos, NM 87545, USA;Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;

关键词: human immunodeficiency virus type 1;    vaccine;    neutralizing antibodies;    immunogen design;    envelope glycoprotein;    coevolution;    immune escape;    quasispecies;    antigenic swarm;    selection;   

DOI  :  10.3390/v7102881

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown