Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) identifies immune-selected HIV variants

Hraber, Peter; Korber, Bette; Wagh, Kshitij; Giorgi, Elena; 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

doi:10.3390/v7102881

Title: Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) identifies immune-selected HIV variants

Journal Article · Wed Oct 21 00:00:00 EDT 2015 · Viruses

DOI:https://doi.org/10.3390/v7102881· OSTI ID:1263552

Hraber, Peter ^[1]; Korber, Bette ^[1]; Wagh, Kshitij ^[1]; Giorgi, Elena ^[1]; Bhattacharya, Tanmoy ^[2]; Gnanakaran, S. ^[1]; Lapedes, Alan S. ^[1]; Learn, Gerald H. ^[3]; Kreider, Edward F. ^[4]; Li, Yingying ^[4]; Shaw, George M. ^[4]; Hahn, Beatrice H. ^[4]; Montefiori, David C. ^[5]; Alam, S. Munir ^[5]; Bonsignori, Mattia ^[5]; Moody, M. Anthony ^[5]; Liao, Hua-Xin ^[5]; Gao, Feng ^[5]; Haynes, Barton ^[5]

Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Santa Fe Inst. (SFI), Santa Fe, NM (United States)
Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine
Univ. of Pennsylvania, Philadelphia, PA (United States). Perelman School of Medicine
Duke Univ. Medical Center, Durham, NC (United States). Duke Human Vaccine Inst.

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. As a result, 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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Research Organization:: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)

Sponsoring Organization:: USDOE; National Institute of Allergy and Infectious Disease (NIAID); National Institutes of Health (NIH)

Grant/Contract Number:: UM1 AI100645; AC52-06NA25396

OSTI ID:: 1263552

Alternate ID(s):: OSTI ID: 1321761

Report Number(s):: LA-UR-15-24067; VIRUBR; PII: v7102881

Journal Information:: Viruses, Vol. 7, Issue 10; ISSN 1999-4915

Publisher:: MDPICopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 20 works

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HIV-1 therapy with monoclonal antibody 3BNC117 elicits host immune responses against HIV-1 Schoofs, T.; Klein, F.; Braunschweig, M. Science, Vol. 352, Issue 6288 https://doi.org/10.1126/science.aaf0972	journal	May 2016
Antigenic Variation and Immune Escape in the MTBC Ernst, Joel D. Strain Variation in the Mycobacterium tuberculosis Complex: Its Role in Biology, Epidemiology and Control https://doi.org/10.1007/978-3-319-64371-7_9	book	January 2017
Long-lasting HIV suppression by combined immunotherapy Jaworski, Juan P. The Lancet HIV, Vol. 5, Issue 12 https://doi.org/10.1016/s2352-3018(18)30294-7	journal	December 2018
Analysis of HIV-1 envelope evolution suggests antibody-mediated selection of common epitopes among Chinese former plasma donors from a narrow-source outbreak Andrews, Sophie M.; Zhang, Yonghong; Dong, Tao Scientific Reports, Vol. 8, Issue 1 https://doi.org/10.1038/s41598-018-23913-2	journal	April 2018
Antibody-virus co-evolution in HIV infection: paths for HIV vaccine development Bonsignori, Mattia; Liao, Hua-Xin; Gao, Feng Immunological Reviews, Vol. 275, Issue 1 https://doi.org/10.1111/imr.12509	journal	January 2017
A de novo approach to inferring within-host fitness effects during untreated HIV-1 infection Illingworth, Christopher J. R.; Raghwani, Jayna; Serwadda, David Apollo - University of Cambridge Repository https://doi.org/10.17863/cam.53933	text	January 2020
HIV Resistance Prediction to Reverse Transcriptase Inhibitors: Focus on Open Data Tarasova, Olga; Poroikov, Vladimir Molecules, Vol. 23, Issue 4 https://doi.org/10.3390/molecules23040956	journal	April 2018
Stabilizing HIV-1 envelope glycoprotein trimers to induce neutralizing antibodies Torrents de la Peña, Alba; Sanders, Rogier W. Retrovirology, Vol. 15, Issue 1 https://doi.org/10.1186/s12977-018-0445-y	journal	September 2018
Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals Bar-On, Yotam; Gruell, Henning; Schoofs, Till Nature Medicine, Vol. 24, Issue 11 https://doi.org/10.1038/s41591-018-0186-4	journal	September 2018
Polyvalent vaccine approaches to combat HIV-1 diversity Korber, Bette; Hraber, Peter; Wagh, Kshitij Immunological Reviews, Vol. 275, Issue 1 https://doi.org/10.1111/imr.12516	journal	January 2017

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59 BASIC BIOLOGICAL SCIENCES
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envelope glycoprotein
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