Design and characterization of an HIV-1 Tat mutant: inactivation of viral and cellular functions but not antigenicity.
Among HIV-1 proteins, Tat is a promising antigen for consideration as a component of anti-HIV-1 vaccine formulations. Nevertheless, this viral protein is able to affect the expression of several cellular genes that are implicated in immune response. In this study, we designed and characterized a mutant form of Tat ("STLA Tat"), which is unable to transactivate viral transcription, and which has lost the deleterious effects on the expression of MHC I, IL-2, and CD25 genes compared with wild-type Tat, as observed in lymphoid Jurkat cells that stably express the tat genes. In vivo experiments in mice revealed that STLA Tat induces anti-Tat antibodies at the same titers as wild-type Tat, which recognize both autologous and heterologous Tat antigens. Finally, STLA Tat did not induce the immunosuppression observed after injection of wild-type Tat. Therefore, this STLA Tat mutant appears to be a safe and promising antigen for further evaluation in anti-HIV-1 vaccine strategies.
Mayol
Katia
K
FRE2736 CNRS/bioMérieux, IFR128 BioSciences Lyon Gerland, 21 avenue Tony Garnier, 69365 Lyon cedex 07, France.
Munier
Séverine
S
Beck
Alain
A
Verrier
Bernard
B
Guillon
Christophe
C
D016915:AIDS Vaccines / Q000276:immunology*; D002460:Cell Line; D005786:Gene Expression Regulation; D015696:Gene Products, tat / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D015488:HIV Antigens / Q000235:genetics* / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics; D009154:Mutation / Q000235:genetics
D016915:AIDS Vaccines; D015696:Gene Products, tat; D015488:HIV Antigens; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit