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Reference: Karlsson, AC, Iversen, AKN, Chapman, JM et al., (2007). Sequential Broadening of CTL Responses in Early HIV-1 Infection Is Associated with Viral Escape. PLOS ONE, 2 (2), e225-e225.Citable link to this page:

 

Sequential Broadening of CTL Responses in Early HIV-1 Infection Is Associated with Viral Escape

Abstract: Background. Antigen-specific CTL responses are thought to play a central role in containment of HIV-1 infection, but no consistent correlation has been found between the magnitude and/or breadth of response and viral load changes during disease progression. Methods and Findings. We undertook a detailed investigation of longitudinal CTL responses and HIV-1 evolution beginning with primary infection in 11 untreated HLA-A2 positive individuals. A subset of patients developed broad responses, which selected for consensus B epitope variants in Gag, Pol, and Nef, suggesting CTL-induced adaptation of HIV-1 at the population level. The patients who developed viral escape mutations and broad autologous CTL responses over time had a significantly higher increase in viral load during the first year of infection compared to those who did not develop viral escape mutations. Conclusions. A continuous dynamic development of CTL responses was associated with viral escape from temporarily effective immune responses. Our results suggest that broad CTL responses often represent footprints left by viral CTL escape rather than effective immune control, and help explain earlier findings that fail to show an association between breadth of CTL responses and viral load. Our results also demonstrate that CTL pressures help to maintain certain elements of consensus viral sequence, which likely represent viral escape from common HLA-restricted CTL responses. The ability of HIV to evolve to escape CTL responses restricted by a common HLA type highlights the challenges posed to development of an effective CTL-based vaccine. © 2007 Karlsson et al.

Peer Review status:Peer reviewedPublication status:PublishedVersion:Publisher's version Funder: NIH   Funder: UCSF/Gladstone Institute of Virology and Immunology Center for AIDS Research   Funder: The Swedish Agency for International Development Cooperation   Notes:Copyright 2007 Karlsson et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Bibliographic Details

Publisher: Public Library of Science

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

Journal: PLOS ONEsee more from them

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

Issue Date: 2007-2-21

pages:Article: e225

pages:e225-e225Identifiers

Urn: uuid:7d44c932-d9fa-461c-ae80-4cc307266e30

Source identifier: 45967

Eissn: 1932-6203

Doi: https://doi.org/10.1371/journal.pone.0000225

Issn: 1932-6203 Item Description

Type: Journal article;

Language: eng

Version: Publisher's version Tiny URL: pubs:45967

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Autor: Karlsson, AC - - - Iversen, AKN - - - Chapman, JM - - - de Oliveira, T - - - Spotts, G - - - Mcmichael, AJ - institutionUniversit

Fuente: https://ora.ox.ac.uk/objects/uuid:7d44c932-d9fa-461c-ae80-4cc307266e30



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