Tat HIV-1 primary and tertiary structures critical to immune response against non-homologous variants.
Clinical studies show that in the absence of anti-retroviral therapy an immune response against the human immunodeficiency virus type 1 (HIV-1), transacting transcriptional activator (Tat) protein correlates with long term non-progression. The purpose of this study is to try to understand what can trigger an effective immune response against Tat. We used five Tat variants from HIV strains identified in different parts of the world and showed that mutations of as much as 38% exist without any change in activity. Rabbit sera were raised against Tat variants identified in rapid-progressor patients (Tat HXB2, a European variant and Tat Eli, an African variant) and a long term non-progressor patient (Tat Oyi, an inactive African variant). Enzyme-linked immunosorbent assay (ELISA) results showed that anti-Tat Oyi serum had the highest antibody titer and was the only one to have a broad antibody response against heterologous Tat variants. Surprisingly, Tat HXB2 was better recognized by anti-Tat Oyi serum compared with anti-Tat HXB2 serum. Western blots showed that non-homologous Tat variants were recognized by antibodies directed against conformational epitopes. This study suggests that the primary and tertiary structures of the Tat variant from the long term non-progressor patient are critical to the induction of a broad and effective antibody response against Tat.
Opi
Sandrine
S
Laboratoire d'Ingénierie des Systèmes Macromoléculaires, Institut de Biologie Structurale et Microbiologie, Centre National de la Recherche Scientifique Unité Propre de Rechereche 9027, 31 Chemin Joseph Aiguier, 13402 Marseille, France.
Péloponèse
Jean-Marie
JM
Esquieu
Didier
D
Campbell
Grant
G
de Mareuil
Jean
J
Walburger
Anne
A
Solomiac
Murielle
M
Grégoire
Catherine
C
Bouveret
Emmanuelle
E
Yirrell
David L
DL
Loret
Erwann P
EP
D016915:AIDS Vaccines / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes; D015696:Gene Products, tat / Q000737:chemistry* / Q000378:metabolism; D015483:HIV Antibodies; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D015533:Transcriptional Activation; D014162:Transfection
D016915:AIDS Vaccines; D000939:Epitopes; D015696:Gene Products, tat; D015483:HIV Antibodies