The Glutamine-rich Region of the HIV-1 Tat Protein Is Involved in T-cell Apoptosis

July 28, 2017

Title

The Glutamine-rich Region of the HIV-1 Tat Protein Is Involved in T-cell Apoptosis

Author

Grant R. Campbell, Eddy Pasquier, Jennifer Watkins, Veronique Bourgarel-Rey, Vincent Peyrot, Didier Esquieu, Pascale Barbier, Jean de Mareuil, Diane Braguer, Pontiano Kaleebu, David L. Yirrell, Erwann P. Loret

Year

2004

Journal

The Journal of Biological Chemistry

Abstract

Human immunodeficiency virus (HIV) infection and the progression to AIDS are characterized by the depletion of CD4+ T-cells. HIV-1 infection leads to apoptosis of uninfected bystander cells and the direct killing of HIV-infected cells. This is mediated, in part, by the HIV-1 Tat protein, which is secreted by virally infected cells and taken up by uninfected cells. We chemically synthesized two 86-residue subtype D Tat proteins, Ug05RP and Ug11LTS, from two Ugandan patients who were clinically categorized as either rapid progressor or long-term survivor, with non-conservative mutations located essentially in the glutamine-rich region. Structural heterogeneities were revealed by CD, which translate into differing trans-activational and apoptotic effects. CD data analysis and molecular modeling indicated that the short α-helix observed in subtype D Tat proteins from rapid progressor patients such as Tat Mal and Tat Ug05RP is not present in Ug11LTS. We show that Tat Ug05RP is more efficient than Tat Ug11LTS in itstrans-activational role and in inducing apoptosis in binding tubulin via the mitochondrial pathway. The glutamine-rich region of Tat appears to be involved in the Tat-mediated apoptosis of T-cells.

Instrument

J-810

Keywords

Circular dichroism, Secondary structure, Biochemistry