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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Sequential broadening of CTL responses in early HIV-1 infection is associated with viral escape
PLoS ONE, Volume 2, No. 2, Article e225, Year 2007
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Description
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.
Authors & Co-Authors
Karlsson, Annika C.
United States, San Francisco
Gladstone Institute of Virology and Immunology
Sweden, Solna
Public Health Agency of Sweden
Iversen, Astrid K.N.
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
De Oliveira, Tulio
United Kingdom, Oxford
University of Oxford
Spotts, Gerald E.
United States, San Francisco
University of California, San Francisco
McMichael, Andrew James
United Kingdom, Oxford
Mrc Weatherall Institute of Molecular Medicine
Davenport, Miles P.
Australia, Sydney
Unsw Sydney
Hecht, Frederick M.
United States, San Francisco
University of California, San Francisco
Nixon, Douglas F.
United States, San Francisco
Gladstone Institute of Virology and Immunology
United States, San Francisco
University of California, San Francisco
Statistics
Citations: 87
Authors: 8
Affiliations: 6
Identifiers
Doi:
10.1371/journal.pone.0000225
ISSN:
19326203
Research Areas
Infectious Diseases
Study Design
Cross Sectional Study
Cohort Study