The HIV‐Tat protein induces chromosome number aberrations by affecting mitosis

Abstract

To analyze the effects of the HIV-Tat-tubulin interaction, we microinjected HIV-Tat purified protein into Drosophila syncytial embryos. Following the Tat injection, altered timing of the cortical nuclear cycles was observed; specifically, the period between the nuclear envelope breakdown and anaphase initiation was lengthened as was the period between anaphase initiation and the formation of the next nuclear envelope. These two periods correspond to kinetochore alignment at metaphase and to mitosis exit, respectively. We also demonstrated that these two delays are the consequence of damage specifically induced by Tat on kinetochore alignment and on the timing of sister chromatid segregation at anaphase. Furthermore, we show that the expression of Tat in Drosophila larvae brain cells produces a significant percentage of polyploid and aneuploid cells. The results reported here indicate that Tat impairs the mitotic process and that Tat-tubulin interaction appears to be responsible for the observed defects. The presence of polyploid and aneuploid cells is consistent with a delay or arrest in the M phase of a substantial fraction of the cells expressing Tat, suggesting that mitotic spindle checkpoints are overridden following Tat expression.

The Ins and Outs of HIV‐1 Tat

“…This interaction has important functional consequences because Tat alters microtubule dynamics and thereby activates a mitochondria‐dependent apoptotic pathway . Tat–tubulin interactions also affect the activity of the mitotic spindle, resulting in defects in chromosome congression and sister chromatid segregation . This delay in polymerization of microtubules also induces mislocalization of several proteins in Drosophila melanogaster oocyte during development .…”

In vivo functional characterization of the SARS-Coronavirus 3a protein in Drosophila

“…Drosophila has been used to study the molecular functions of various viral gene products [16][17][18]. For example, the HIV-1 Tat protein was first found to interact with tubulin in Drosophila [16] and such interaction has subsequently been demonstrated in mammalian cells [19].…”

Effects of viral proteins on the nuclear organization of human peripheral blood B-cells

“…Le rôle de la protéine Tat dans l'induction des aberrations chromosomiques au niveau des cellules ou systèmes humains n'a été jamais étudié. Une seule étude sur le rôle de Tat dans l'induction des aberrations au niveau de nombreux chromosomes, a été étudié sur des embryons de Drosophila injectés par la protéine purifiée Tat du VIH-1 (Battaglia et al, 2005). Nous avons pu montrer le rôle de la protéine oncogénique d'une autre façon, en étudiant son effet sur l'induction des aberrations chromosomiques dans les lignées cellulaires lymphoblastoïdes RPMI 8866, dont plusieurs anomalies chromosomiques ont été détectées suite à l'analyse de caryotype.…”