A Drosophila model of HIV-Tat-related pathogenicity.
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.
Battaglia
P A
PA
Laboratorio di Biologia Cellulare, Istituto Superiore di Sanità, Rome, Italy.
Zito
S
S
Macchini
A
A
Gigliani
F
F
D000818:Animals; D030801:Animals, Genetically Modified; D015153:Blotting, Western; D016764:Cell Polarity; D003593:Cytoplasm / Q000378:metabolism / Q000821:virology; D019281:Dimerization; D004195:Disease Models, Animal; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000821:virology*; D005260:Female; D015696:Gene Products, tat / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D006678:HIV / Q000472:pathogenicity*; D015658:HIV Infections / Q000503:physiopathology*; D008297:Male; D008870:Microtubules / Q000378:metabolism; D009865:Oocytes / Q000821:virology; D011108:Polymers / Q000378:metabolism; D013090:Spermatocytes / Q000821:virology; D019076:Transgenes / Q000502:physiology; D014404:Tubulin / Q000032:analysis / Q000378:metabolism; D014774:Virulence; D054322:tat Gene Products, Human Immunodeficiency Virus
D015696:Gene Products, tat; D011108:Polymers; D014404:Tubulin; D054322:tat Gene Products, Human Immunodeficiency Virus