Gag-specific CD8+ T lymphocytes recognize infected cells before AIDS-virus integration and viral protein expression.
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.
Sacha
Jonah B
JB
Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53711, USA.
Chung
Chungwon
C
Rakasz
Eva G
EG
Spencer
Sean P
SP
Jonas
Anna K
AK
Bean
Alexander T
AT
Lee
Wonhee
W
Burwitz
Benjamin J
BJ
Stephany
Jason J
JJ
Loffredo
John T
JT
Allison
David B
DB
Adnan
Sama
S
Hoji
Akihiko
A
Wilson
Nancy A
NA
Friedrich
Thomas C
TC
Lifson
Jeffrey D
JD
Yang
Otto O
OO
Watkins
David I
DI
D016915:AIDS Vaccines / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000276:immunology*; D015683:Gene Products, gag / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology; D008253:Macaca mulatta; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013997:Time Factors; D016662:Virus Integration / Q000276:immunology*
D016915:AIDS Vaccines; D018984:Epitopes, T-Lymphocyte; D015683:Gene Products, gag; D015395:Histocompatibility Antigens Class I