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Infectious Disorders - Drug Targets


ISSN (Print): 1871-5265
ISSN (Online): 2212-3989

HIV-1 Infected Patients have Antibodies Recognizing Folded Tat

Author(s): Sonia Mediouni, Gilbert Baillat, Albert Darque, Isabelle Ravaux and Erwann Loret

Volume 11, Issue 1, 2011

Page: [57 - 63] Pages: 7

DOI: 10.2174/187152611794407737

Price: $65


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.

Keywords: Antibodies, HIV-1, infected patients, Oyi, Tat, vaccine, regulatory viral protein, transactivator of HIV-1 genes, apoptosis, indirect ELISA method, tubulins, mitochondrial apoptosis, therapeutic vaccine, Mutations, epitope, neutralizing antibodies against Tat variants, Transactivation Assay with HeLa Cells, Dulbecco's Modified Eagles Medium (DMEM), Bovine Serum Albumin, Sigma-Aldrich, Human Sera, Dot Blot Assay, nitro-cellulose membranes, diaminobenzidine tetra, PBS buffer, Rabbit sera

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