title: HIV-1 infected patients have antibodies recognizing folded Tat.
abstract: Tat is a regulatory viral protein known as transactivator of HIV-1 genes but Tat is also secreted in the blood from HIV-1 infected cells. Extra cellular Tat can cross cellular membranes to trigger apoptosis and might explain the incapacity of the cellular immunity to eliminate HIV-1 infected cells. There is a controversy regarding Tat structure with studies suggesting that Tat would be a naturally unfolded protein. Here, we show that synthetic Tat variants need to be folded to have a transactivation activity in a cellular assay but this folding is unstable regarding the buffers and/or pH used as solvent. We show also that the recognition of a Tat variant versus peptides, covering its sequence, was different. Using an indirect ELISA method with 40 sera from volunteer HIV-1 infected patients, we show that Tat was recognized by 19 human sera either exclusively (n=8) or with Tat peptides (n=11). Dot Blot showed that unfolded Tat was no longer detectable by sera of the first group (n=8) compared to folded Tat. As a conclusion, this study suggests that Tat could be a naturally folded protein in the blood of HIV infected patients.
authors.affiliation: Equipe de Recherche Technologique 2011, Faculté de Pharmacie, 27 BD Jean Moulin, 13385 Marseille, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Mediouni
authors.forename: Gilbert
authors.initials: G
authors.lastname: Baillat
authors.forename: Albert
authors.initials: A
authors.lastname: Darque
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ravaux
authors.forename: Erwann
authors.initials: E
authors.lastname: Loret
mesh_terms: D004797:Enzyme-Linked Immunosorbent Assay; D015483:HIV Antibodies / Q000096:biosynthesis / Q000097:blood / Q000737:chemistry / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D017510:Protein Folding; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000096:biosynthesis / Q000737:chemistry / Q000276:immunology*
chemical_list: D015483:HIV Antibodies; D054322:tat Gene Products, Human Immunodeficiency Virus