Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression |
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Authors: | Sacha Jonah B Chung Chungwon Rakasz Eva G Spencer Sean P Jonas Anna K Bean Alexander T Lee Wonhee Burwitz Benjamin J Stephany Jason J Loffredo John T Allison David B Adnan Sama Hoji Akihiko Wilson Nancy A Friedrich Thomas C Lifson Jeffrey D Yang Otto O Watkins David I |
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Institution: | Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53711, USA. |
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Abstract: | CD8(+) T cells are a key focus of vaccine development efforts for HIV. However, there is no clear consensus as to which of the nine HIV proteins should be used for vaccination. The early proteins Tat, Rev, and Nef may be better CD8(+) T cell targets than the late-expressed structural proteins Gag, Pol, and Env. In this study, we show that Gag-specific CD8(+) T cells recognize infected CD4(+) T lymphocytes as early as 2 h postinfection, before proviral DNA integration, viral protein synthesis, and Nef-mediated MHC class I down-regulation. Additionally, the number of Gag epitopes recognized by CD8(+) T cells was significantly associated with lower viremia (p = 0.0017) in SIV-infected rhesus macaques. These results suggest that HIV vaccines should focus CD8(+) T cell responses on Gag. |
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