CD8+ T cells from SIV elite controller macaques recognize Mamu-B*08-bound epitopes and select for widespread viral variation.
<h4>Background</h4>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 individua...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2007-11-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001152&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1825206824970747904 |
|---|---|
| author | John T Loffredo Thomas C Friedrich Enrique J León Jason J Stephany Denise S Rodrigues Sean P Spencer Alex T Bean Dominic R Beal Benjamin J Burwitz Richard A Rudersdorf Lyle T Wallace Shari M Piaskowski Gemma E May John Sidney Emma Gostick Nancy A Wilson David A Price Esper G Kallas Helen Piontkivska Austin L Hughes Alessandro Sette David I Watkins |
| author_facet | John T Loffredo Thomas C Friedrich Enrique J León Jason J Stephany Denise S Rodrigues Sean P Spencer Alex T Bean Dominic R Beal Benjamin J Burwitz Richard A Rudersdorf Lyle T Wallace Shari M Piaskowski Gemma E May John Sidney Emma Gostick Nancy A Wilson David A Price Esper G Kallas Helen Piontkivska Austin L Hughes Alessandro Sette David I Watkins |
| author_sort | John T Loffredo |
| collection | DOAJ |
| description | <h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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 | Article |
| id | doaj-art-d08238c326d940c8b261ff79190160fc |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2007-11-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-d08238c326d940c8b261ff79190160fc2025-02-07T05:30:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-11-01211e115210.1371/journal.pone.0001152CD8+ T cells from SIV elite controller macaques recognize Mamu-B*08-bound epitopes and select for widespread viral variation.John T LoffredoThomas C FriedrichEnrique J LeónJason J StephanyDenise S RodriguesSean P SpencerAlex T BeanDominic R BealBenjamin J BurwitzRichard A RudersdorfLyle T WallaceShari M PiaskowskiGemma E MayJohn SidneyEmma GostickNancy A WilsonDavid A PriceEsper G KallasHelen PiontkivskaAustin L HughesAlessandro SetteDavid I Watkins<h4>Background</h4>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.<h4>Methods and findings</h4>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.<h4>Conclusions</h4>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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001152&type=printable |
| spellingShingle | John T Loffredo Thomas C Friedrich Enrique J León Jason J Stephany Denise S Rodrigues Sean P Spencer Alex T Bean Dominic R Beal Benjamin J Burwitz Richard A Rudersdorf Lyle T Wallace Shari M Piaskowski Gemma E May John Sidney Emma Gostick Nancy A Wilson David A Price Esper G Kallas Helen Piontkivska Austin L Hughes Alessandro Sette David I Watkins CD8+ T cells from SIV elite controller macaques recognize Mamu-B*08-bound epitopes and select for widespread viral variation. PLoS ONE |
| 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 |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0001152&type=printable |
| work_keys_str_mv | AT johntloffredo cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT thomascfriedrich cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT enriquejleon cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT jasonjstephany cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT denisesrodrigues cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT seanpspencer cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT alextbean cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT dominicrbeal cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT benjaminjburwitz cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT richardarudersdorf cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT lyletwallace cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT sharimpiaskowski cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT gemmaemay cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT johnsidney cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT emmagostick cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT nancyawilson cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT davidaprice cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT espergkallas cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT helenpiontkivska cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT austinlhughes cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT alessandrosette cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation AT davidiwatkins cd8tcellsfromsivelitecontrollermacaquesrecognizemamub08boundepitopesandselectforwidespreadviralvariation |