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CD8(+) T Cells from SIV Elite Controller Macaques Recognize Mamu-B*08-Bound Epitopes and Select for Widespread Viral Variation
BACKGROUND: It is generally accepted that CD8(+) T cell responses play an important role in control of immunodeficiency virus replication. The association of HLA-B27 and -B57 with control of viremia supports this conclusion. However, specific correlates of viral control in individuals expressing the...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2007
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2062500/ https://www.ncbi.nlm.nih.gov/pubmed/18000532 http://dx.doi.org/10.1371/journal.pone.0001152 |
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author | Loffredo, John T. Friedrich, Thomas C. León, Enrique J. Stephany, Jason J. Rodrigues, Denise S. Spencer, Sean P. Bean, Alex T. Beal, Dominic R. Burwitz, Benjamin J. Rudersdorf, Richard A. Wallace, Lyle T. Piaskowski, Shari M. May, Gemma E. Sidney, John Gostick, Emma Wilson, Nancy A. Price, David A. Kallas, Esper G. Piontkivska, Helen Hughes, Austin L. Sette, Alessandro Watkins, David I. |
author_facet | Loffredo, John T. Friedrich, Thomas C. León, Enrique J. Stephany, Jason J. Rodrigues, Denise S. Spencer, Sean P. Bean, Alex T. Beal, Dominic R. Burwitz, Benjamin J. Rudersdorf, Richard A. Wallace, Lyle T. Piaskowski, Shari M. May, Gemma E. Sidney, John Gostick, Emma Wilson, Nancy A. Price, David A. Kallas, Esper G. Piontkivska, Helen Hughes, Austin L. Sette, Alessandro Watkins, David I. |
author_sort | Loffredo, John T. |
collection | PubMed |
description | BACKGROUND: It is generally accepted that CD8(+) T cell responses play an important role in control of immunodeficiency virus replication. The association of HLA-B27 and -B57 with control of viremia supports this conclusion. However, specific correlates of viral control in individuals expressing these alleles have been difficult to define. We recently reported that transient in vivo CD8(+) cell depletion in simian immunodeficiency virus (SIV)-infected elite controller (EC) macaques resulted in a brief period of viral recrudescence. SIV replication was rapidly controlled with the reappearance of CD8(+) cells, implicating that these cells actively suppress viral replication in ECs. METHODS AND FINDINGS: Here we show that three ECs in that study made at least seven robust CD8(+) T cell responses directed against novel epitopes in Vif, Rev, and Nef restricted by the MHC class I molecule Mamu-B*08. Two of these Mamu-B*08-positive animals subsequently lost control of SIV replication. Their breakthrough virus harbored substitutions in multiple Mamu-B*08-restricted epitopes. Indeed, we found evidence for selection pressure mediated by Mamu-B*08-restricted CD8(+) T cells in all of the newly identified epitopes in a cohort of chronically infected macaques. CONCLUSIONS: Together, our data suggest that Mamu-B*08-restricted CD8(+) T cell responses effectively control replication of pathogenic SIV(mac)239. All seven regions encoding Mamu-B*08-restricted CD8(+) T cell epitopes also exhibit amino acid replacements typically seen only in the presence of Mamu-B*08, suggesting that the variation we observe is indeed selected by CD8(+) T cell responses. SIV(mac)239 infection of Indian rhesus macaques expressing Mamu-B*08 may therefore provide an animal model for understanding CD8(+) T cell-mediated control of HIV replication in humans. |
format | Text |
id | pubmed-2062500 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-20625002007-11-14 CD8(+) T Cells from SIV Elite Controller Macaques Recognize Mamu-B*08-Bound Epitopes and Select for Widespread Viral Variation Loffredo, John T. Friedrich, Thomas C. León, Enrique J. Stephany, Jason J. Rodrigues, Denise S. Spencer, Sean P. Bean, Alex T. Beal, Dominic R. Burwitz, Benjamin J. Rudersdorf, Richard A. Wallace, Lyle T. Piaskowski, Shari M. May, Gemma E. Sidney, John Gostick, Emma Wilson, Nancy A. Price, David A. Kallas, Esper G. Piontkivska, Helen Hughes, Austin L. Sette, Alessandro Watkins, David I. PLoS One Research Article BACKGROUND: It is generally accepted that CD8(+) T cell responses play an important role in control of immunodeficiency virus replication. The association of HLA-B27 and -B57 with control of viremia supports this conclusion. However, specific correlates of viral control in individuals expressing these alleles have been difficult to define. We recently reported that transient in vivo CD8(+) cell depletion in simian immunodeficiency virus (SIV)-infected elite controller (EC) macaques resulted in a brief period of viral recrudescence. SIV replication was rapidly controlled with the reappearance of CD8(+) cells, implicating that these cells actively suppress viral replication in ECs. METHODS AND FINDINGS: Here we show that three ECs in that study made at least seven robust CD8(+) T cell responses directed against novel epitopes in Vif, Rev, and Nef restricted by the MHC class I molecule Mamu-B*08. Two of these Mamu-B*08-positive animals subsequently lost control of SIV replication. Their breakthrough virus harbored substitutions in multiple Mamu-B*08-restricted epitopes. Indeed, we found evidence for selection pressure mediated by Mamu-B*08-restricted CD8(+) T cells in all of the newly identified epitopes in a cohort of chronically infected macaques. CONCLUSIONS: Together, our data suggest that Mamu-B*08-restricted CD8(+) T cell responses effectively control replication of pathogenic SIV(mac)239. All seven regions encoding Mamu-B*08-restricted CD8(+) T cell epitopes also exhibit amino acid replacements typically seen only in the presence of Mamu-B*08, suggesting that the variation we observe is indeed selected by CD8(+) T cell responses. SIV(mac)239 infection of Indian rhesus macaques expressing Mamu-B*08 may therefore provide an animal model for understanding CD8(+) T cell-mediated control of HIV replication in humans. Public Library of Science 2007-11-14 /pmc/articles/PMC2062500/ /pubmed/18000532 http://dx.doi.org/10.1371/journal.pone.0001152 Text en Loffredo et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Loffredo, John T. Friedrich, Thomas C. León, Enrique J. Stephany, Jason J. Rodrigues, Denise S. Spencer, Sean P. Bean, Alex T. Beal, Dominic R. Burwitz, Benjamin J. Rudersdorf, Richard A. Wallace, Lyle T. Piaskowski, Shari M. May, Gemma E. Sidney, John Gostick, Emma Wilson, Nancy A. Price, David A. Kallas, Esper G. Piontkivska, Helen Hughes, Austin L. Sette, Alessandro Watkins, David I. CD8(+) T Cells from SIV Elite Controller Macaques Recognize Mamu-B*08-Bound Epitopes and Select for Widespread Viral Variation |
title | CD8(+) T Cells from SIV Elite Controller Macaques Recognize Mamu-B*08-Bound Epitopes and Select for Widespread Viral Variation |
title_full | CD8(+) T Cells from SIV Elite Controller Macaques Recognize Mamu-B*08-Bound Epitopes and Select for Widespread Viral Variation |
title_fullStr | CD8(+) T Cells from SIV Elite Controller Macaques Recognize Mamu-B*08-Bound Epitopes and Select for Widespread Viral Variation |
title_full_unstemmed | CD8(+) T Cells from SIV Elite Controller Macaques Recognize Mamu-B*08-Bound Epitopes and Select for Widespread Viral Variation |
title_short | CD8(+) T Cells from SIV Elite Controller Macaques Recognize Mamu-B*08-Bound Epitopes and Select for Widespread Viral Variation |
title_sort | cd8(+) t cells from siv elite controller macaques recognize mamu-b*08-bound epitopes and select for widespread viral variation |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2062500/ https://www.ncbi.nlm.nih.gov/pubmed/18000532 http://dx.doi.org/10.1371/journal.pone.0001152 |
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