Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection.

In the present study, we analyzed the functional profile of CD8+ T-cell responses directed against autologous transmitted/founder HIV-1 isolates during acute and early infection, and examined whether multifunctionality is required for selection of virus escape mutations. Seven anti-retroviral therap...

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Autores principales:	Guido Ferrari, Bette Korber, Nilu Goonetilleke, Michael K P Liu, Emma L Turnbull, Jesus F Salazar-Gonzalez, Natalie Hawkins, Steve Self, Sydeaka Watson, Michael R Betts, Cynthia Gay, Kara McGhee, Pierre Pellegrino, Ian Williams, Georgia D Tomaras, Barton F Haynes, Clive M Gray, Persephone Borrow, Mario Roederer, Andrew J McMichael, Kent J Weinhold
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a23efb6b873d445da5c85d22e3a5462f
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spelling	oai:doaj.org-article:a23efb6b873d445da5c85d22e3a5462f2021-11-18T06:03:37ZRelationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection.1553-73661553-737410.1371/journal.ppat.1001273https://doaj.org/article/a23efb6b873d445da5c85d22e3a5462f2011-02-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21347345/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374In the present study, we analyzed the functional profile of CD8+ T-cell responses directed against autologous transmitted/founder HIV-1 isolates during acute and early infection, and examined whether multifunctionality is required for selection of virus escape mutations. Seven anti-retroviral therapy-naïve subjects were studied in detail between 1 and 87 weeks following onset of symptoms of acute HIV-1 infection. Synthetic peptides representing the autologous transmitted/founder HIV-1 sequences were used in multiparameter flow cytometry assays to determine the functionality of HIV-1-specific CD8+ T memory cells. In all seven patients, the earliest T cell responses were predominantly oligofunctional, although the relative contribution of multifunctional cell responses increased significantly with time from infection. Interestingly, only the magnitude of the total and not of the poly-functional T-cell responses was significantly associated with the selection of escape mutants. However, the high contribution of MIP-1β-producing CD8+ T-cells to the total response suggests that mechanisms not limited to cytotoxicity could be exerting immune pressure during acute infection. Lastly, we show that epitope entropy, reflecting the capacity of the epitope to tolerate mutational change and defined as the diversity of epitope sequences at the population level, was also correlated with rate of emergence of escape mutants.Guido FerrariBette KorberNilu GoonetillekeMichael K P LiuEmma L TurnbullJesus F Salazar-GonzalezNatalie HawkinsSteve SelfSydeaka WatsonMichael R BettsCynthia GayKara McGheePierre PellegrinoIan WilliamsGeorgia D TomarasBarton F HaynesClive M GrayPersephone BorrowMario RoedererAndrew J McMichaelKent J WeinholdPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 7, Iss 2, p e1001273 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Guido Ferrari Bette Korber Nilu Goonetilleke Michael K P Liu Emma L Turnbull Jesus F Salazar-Gonzalez Natalie Hawkins Steve Self Sydeaka Watson Michael R Betts Cynthia Gay Kara McGhee Pierre Pellegrino Ian Williams Georgia D Tomaras Barton F Haynes Clive M Gray Persephone Borrow Mario Roederer Andrew J McMichael Kent J Weinhold Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection.
description	In the present study, we analyzed the functional profile of CD8+ T-cell responses directed against autologous transmitted/founder HIV-1 isolates during acute and early infection, and examined whether multifunctionality is required for selection of virus escape mutations. Seven anti-retroviral therapy-naïve subjects were studied in detail between 1 and 87 weeks following onset of symptoms of acute HIV-1 infection. Synthetic peptides representing the autologous transmitted/founder HIV-1 sequences were used in multiparameter flow cytometry assays to determine the functionality of HIV-1-specific CD8+ T memory cells. In all seven patients, the earliest T cell responses were predominantly oligofunctional, although the relative contribution of multifunctional cell responses increased significantly with time from infection. Interestingly, only the magnitude of the total and not of the poly-functional T-cell responses was significantly associated with the selection of escape mutants. However, the high contribution of MIP-1β-producing CD8+ T-cells to the total response suggests that mechanisms not limited to cytotoxicity could be exerting immune pressure during acute infection. Lastly, we show that epitope entropy, reflecting the capacity of the epitope to tolerate mutational change and defined as the diversity of epitope sequences at the population level, was also correlated with rate of emergence of escape mutants.
format	article
author	Guido Ferrari Bette Korber Nilu Goonetilleke Michael K P Liu Emma L Turnbull Jesus F Salazar-Gonzalez Natalie Hawkins Steve Self Sydeaka Watson Michael R Betts Cynthia Gay Kara McGhee Pierre Pellegrino Ian Williams Georgia D Tomaras Barton F Haynes Clive M Gray Persephone Borrow Mario Roederer Andrew J McMichael Kent J Weinhold
author_facet	Guido Ferrari Bette Korber Nilu Goonetilleke Michael K P Liu Emma L Turnbull Jesus F Salazar-Gonzalez Natalie Hawkins Steve Self Sydeaka Watson Michael R Betts Cynthia Gay Kara McGhee Pierre Pellegrino Ian Williams Georgia D Tomaras Barton F Haynes Clive M Gray Persephone Borrow Mario Roederer Andrew J McMichael Kent J Weinhold
author_sort	Guido Ferrari
title	Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection.
title_short	Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection.
title_full	Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection.
title_fullStr	Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection.
title_full_unstemmed	Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection.
title_sort	relationship between functional profile of hiv-1 specific cd8 t cells and epitope variability with the selection of escape mutants in acute hiv-1 infection.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/a23efb6b873d445da5c85d22e3a5462f
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Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection.

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