A Drosophila model of HIV-Tat-related pathogenicity
Author:
Battaglia Piero A.1, Zito Santina2, Macchini Antonella1, Gigliani Franca23
Affiliation:
1. Laboratorio di Biologia Cellulare, Istituto Superiore di Sanità, Rome, Italy 2. Dipartimento di Biotechnologie Cellulari ed Ematologia, Università La Sapienza, Rome, Italy 3. Author for correspondence (e-mail: Gigliani@bce.med.uniroma1.it )
Abstract
To analyze the mechanism of Tat-mediated HIV pathogenicity, we produced a Drosophila melanogaster strain transgenic for HIV-tat gene and induced the expression of the protein during Drosophila development. By in vitro and in vivo experiments, we demonstrated that Tat specifically binds to tubulin via the MAP-binding domain of tubulin, and that this interaction delays the polymerization of tubulin and induces a premature stop to microtubule-dependent cytoplasmic streaming. The delay in the polymerization of microtubules, the tracks for the transport of the axes determinants, alters the positioning of the dorso-ventral axis as shown by the mislocalization of Gurken and Kinesin in oocyte of Drosophila after Tat induction. These results validate the use of Drosophila as a tool to study the molecular mechanism of viral gene products and suggest that Tat-tubulin interaction is responsible for neurodegenerative diseases associated with AIDS.
Publisher
The Company of Biologists
Reference44 articles.
1. Battaglia, P. A., Regoli, E. and Gigliani F. (1997). Measurement of the range of HIV-LTR transactivating activity of HIV-TAT in vitro. Int. J. Oncology. 11, 1007-1011. 2. Benelli, R., Barbero, A., Ferrini, S., Scapini, P., Cassatella, M., Bussolino, F., Tacchetti, C., Noonan, D. M. and Albini, A. (2000). Human immunodeficiency virus transactivator protein (Tat) stimulates chemotaxis, calcium mobilization, and activation of human polymorphonuclear leukocytes: implications for Tat-mediated pathogenesis. J. Infect. Dis.182, 1643-1651. 3. Bukrinskaya, A., Brichacek, B., Mann, A. and Stevenson, M. (1998). Establishment of a functional human immunodeficiency virus type 1 (HIV-1) reverse transcription complex involves the cytoskeleton. J. Exp. Med.188, 2113-2125. 4. Cenacchi, G., Guiducci, G., Pasquinelli, G., Re, M. C., Ramazzotti, E., Furlini, G., Malorni, W., DeLuca, M. and Martinelli, G. N. (1996). Early ultrastructural changes of human keratinocytes after HIV-1 contact: an in vitro study. Eur. J. Dermatol. 6, 213-218. 5. Chang, H. K., Gallo, R. C. and Ensoli, B. (1995). Regulation of cellular gene expression and function by tha human immunodeficiency virus type-1 Tat protein. J. Biomed. Sci.2, 189-202.
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