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.Reportar como inadecuado




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Reference: Ferrari, G, Korber, B, Goonetilleke, N et al., (2011). 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. PLoS pathogens, 7 (2), e1001273.Citable link to this page:

 

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.

Abstract: 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.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's version Funder: Duke University Center for AIDS Research   Funder: Center for HIV/AIDS Vaccine Immunology   Funder: National Institutes of Health   Funder: Bill and Melinda Gates Foundation   Notes:This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

Bibliographic Details

Publisher: Public Library of Science

Publisher Website: http://www.plos.org/

Journal: PLoS pathogenssee more from them

Publication Website: http://www.plospathogens.org/

Issue Date: 2011

pages:e1001273Identifiers

Urn: uuid:75b4a862-44d2-47b2-a7f8-0d576bd8ac90

Source identifier: 120166

Eissn: 1553-7374

Doi: https://doi.org/10.1371/journal.ppat.1001273

Issn: 1553-7366 Item Description

Type: Journal article;

Language: eng

Version: Publisher's versionKeywords: Humans CD8-Positive T-Lymphocytes HIV Infections Epitopes Mutation Antigenic Variation Adult Immunologic Memory Selection, Genetic HIV-1 Immune Evasion Middle Aged Young Adult Organisms, Genetically Modified Male Tiny URL: pubs:120166

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Autor: Ferrari, G - - - Korber, B - - - Goonetilleke, N - institutionUniversity of Oxford - - - Liu, MK - institutionUniversity of Oxfor

Fuente: https://ora.ox.ac.uk/objects/uuid:75b4a862-44d2-47b2-a7f8-0d576bd8ac90



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