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Published in: Medical Microbiology and Immunology 2/2012

01-05-2012 | Original Investigation

Control of M184V HIV-1 mutants by CD8 T-cell responses

Authors: Thomas Vollbrecht, Josef Eberle, Julia Roider, Silja Bühler, Renate Stirner, Nadja Henrich, Ulrich Seybold, Johannes R. Bogner, Rika Draenert

Published in: Medical Microbiology and Immunology | Issue 2/2012

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Abstract

Antiretroviral treatment directed against HIV is highly effective, yet limited by drug resistance mutations. We hypothesized that CD8 T cells targeting drug-resistant HIV mutants are able to inhibit viral replication in the setting of a failing therapeutic regimen. We evaluated CD8 T-cell responses and mapped epitopes in HIV-infected patients by interferon-gamma Elispot and intracellular cytokine staining. Autologous virus was sequenced by RT-PCR. Viral replication inhibition assays were performed using M184V mutant virus and CD8 T cell lines. CD8 T-cell responses toward the regions of viral drug resistance mutations in Pol are frequent. Focusing on the M184V mutation, A*02:01-YQYVDDLYV and A*02:01-VIYQYVDDLYV were identified as optimal epitopes for the majority of study subjects. Viral replication of M184V HIV mutants was inhibited by CD8 T cell lines in vitro. In case of a failing lamivudine/emtricitabine containing regimen, individuals with a CD8 T-cell response toward M184V had a significant lower viral load than those without a CD8 response (p = 0.005). Two study subjects even achieved an undetectable viral load. Our data suggest that control of M184V mutant virus by CD8 T-cell responses is possible in vitro and in vivo. This control has important implications for therapeutic vaccination strategies.
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Science 330(6010):1551–1557. doi:10.​1126/​science.​1195271
Metadata
Title
Control of M184V HIV-1 mutants by CD8 T-cell responses
Authors
Thomas Vollbrecht
Josef Eberle
Julia Roider
Silja Bühler
Renate Stirner
Nadja Henrich
Ulrich Seybold
Johannes R. Bogner
Rika Draenert
Publication date
01-05-2012
Publisher
Springer-Verlag
Published in
Medical Microbiology and Immunology / Issue 2/2012
Print ISSN: 0300-8584
Electronic ISSN: 1432-1831
DOI
https://doi.org/10.1007/s00430-011-0222-1

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