Within-Epitope Interactions Can Bias CTL Escape Estimation in Early HIV Infection

Frontiers in Immunology
Victor Garcia, Marcus W Feldman

Abstract

As human immunodeficiency virus (HIV) begins to replicate within hosts, immune responses are elicited against it. Escape mutations in viral epitopes-immunogenic peptide parts presented on the surface of infected cells-allow HIV to partially evade these responses, and thus rapidly go to fixation. The faster they go to fixation, i.e., the higher their escape rate, the larger the selective pressure exerted by the immune system is assumed to be. This relation underpins the rationale for using escapes to assess the strength of immune responses. However, escape rate estimates are often obtained by employing an aggregation procedure, where several mutations that affect the same epitope are aggregated into a single, composite epitope mutation. The aggregation procedure thus rests upon the assumption that all within-epitope mutations have indistinguishable effects on immune recognition. In this study, we investigate how violation of this assumption affects escape rate estimates. To this end, we extend a previously developed simulation model of HIV that accounts for mutation, selection, and recombination to include different distributions of fitness effects (DFEs) and inter-mutational genomic distances. We use this discrete time Wright-F...Continue Reading

References

Mar 3, 1999·Proceedings of the National Academy of Sciences of the United States of America·A G RodrigoJ I Mullins
Jan 11, 2000·Journal of Virology·A E JetztJ P Dougherty
Nov 17, 2004·The Journal of Experimental Medicine·Nicola A JonesPersephone Borrow
Apr 11, 2006·PLoS Computational Biology·Vitaly V Ganusov, Rob J De Boer
Jul 19, 2008·PLoS Computational Biology·Christian L Althaus, Rob J De Boer
May 21, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Emma L TurnbullPersephone Borrow
Jun 3, 2009·The Journal of Experimental Medicine·Nilu GoonetillekeAndrew J McMichael
Jun 3, 2009·The Journal of Experimental Medicine·Jesus F Salazar-GonzalezGeorge M Shaw
Aug 8, 2009·Journal of Theoretical Biology·Ha Youn LeeAlan S Perelson
Dec 17, 2009·Nature Reviews. Immunology·Andrew J McMichaelBarton F Haynes
Feb 4, 2010·PLoS Computational Biology·Richard A Neher, Thomas Leitner
Sep 25, 2010·The Journal of Infectious Diseases·Christian L BoutwellTodd M Allen
Feb 2, 2011·PloS One·Yi LiuJames I Mullins
Mar 29, 2011·Nature Genetics·Trevor HinkleySebastian Bonhoeffer
Sep 20, 2011·Genetics·Stephan SchiffelsMichael Lässig
Oct 21, 2011·Journal of Virology·Shelby L O'ConnorDavid H O'Connor
Jan 3, 2012·Genetics·Jack da Silva
Mar 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Benjamin H GoodMichael M Desai
Oct 26, 2012·Bioinformatics·Fabio Zanini, Richard A Neher
Dec 12, 2012·The Journal of Clinical Investigation·Michael K P LiuNilu Goonetilleke
Aug 14, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Hanneke W M van DeutekomRob J de Boer
Sep 12, 2013·BMC Biology·Alan S Perelson, Ruy M Ribeiro
Sep 13, 2013·Frontiers in Immunology·Taylor A KessingerRichard A Neher
Jan 1, 2013·Journal of Statistical Mechanics : Theory and Experiment·Vitaly V GanusovAlan S Perelson
Apr 5, 2014·PLoS Computational Biology·Marjet ElemansBecca Asquith
Jan 30, 2015·Frontiers in Immunology·Victor Garcia, Roland Robert Regoes
Feb 3, 2015·PLoS Genetics·Hannah E RobertsUNKNOWN SPARTAC trial investigators
Oct 28, 2015·PLoS Computational Biology·Sivan Leviyang, Vitaly V Ganusov

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Citations

Mar 23, 2018·Journal of the Royal Society, Interface·Victor GarciaMarcus W Feldman

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