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

Publication ,  Journal Article
Hraber, P; Korber, B; Wagh, K; Giorgi, EE; Bhattacharya, T; Gnanakaran, S; Lapedes, AS; Learn, GH; Kreider, EF; Li, Y; Shaw, GM; Hahn, BH ...
Published in: Viruses
October 21, 2015

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.

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Published In

Viruses

DOI

EISSN

1999-4915

Publication Date

October 21, 2015

Volume

7

Issue

10

Start / End Page

5443 / 5475

Location

Switzerland

Related Subject Headings

  • Virology
  • Selection, Genetic
  • Longitudinal Studies
  • Immune Evasion
  • Humans
  • HIV Infections
  • HIV
  • Genetic Variation
  • Antigens, Viral
  • 3107 Microbiology
 

Citation

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Hraber, P., Korber, B., Wagh, K., Giorgi, E. E., Bhattacharya, T., Gnanakaran, S., … Haynes, B. F. (2015). Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants. Viruses, 7(10), 5443–5475. https://doi.org/10.3390/v7102881
Hraber, Peter, Bette Korber, Kshitij Wagh, Elena E. Giorgi, Tanmoy Bhattacharya, S. Gnanakaran, Alan S. Lapedes, et al. “Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants.Viruses 7, no. 10 (October 21, 2015): 5443–75. https://doi.org/10.3390/v7102881.
Hraber P, Korber B, Wagh K, Giorgi EE, Bhattacharya T, Gnanakaran S, et al. Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants. Viruses. 2015 Oct 21;7(10):5443–75.
Hraber, Peter, et al. “Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants.Viruses, vol. 7, no. 10, Oct. 2015, pp. 5443–75. Pubmed, doi:10.3390/v7102881.
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 H-X, Gao F, Haynes BF. Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) Identifies Immune-Selected HIV Variants. Viruses. 2015 Oct 21;7(10):5443–5475.

Published In

Viruses

DOI

EISSN

1999-4915

Publication Date

October 21, 2015

Volume

7

Issue

10

Start / End Page

5443 / 5475

Location

Switzerland

Related Subject Headings

  • Virology
  • Selection, Genetic
  • Longitudinal Studies
  • Immune Evasion
  • Humans
  • HIV Infections
  • HIV
  • Genetic Variation
  • Antigens, Viral
  • 3107 Microbiology