D'Agostino D M, Zotti L, Ferro T, Franchini G, Chieco-Bianchi L, Ciminale V
Department of Oncology and Surgical Sciences, University of Padova, I-35128 Padua, Italy.
AIDS Res Hum Retroviruses. 2000 Nov 1;16(16):1765-70. doi: 10.1089/08892220050193281.
In addition to the essential regulatory proteins Rex and Tax, the HTLV-1 genome encodes several accessory proteins of yet undefined function. One of these "orphan" proteins, named p13(II), was recently shown to be selectively targeted to mitochondria and to induce specific changes in mitochondrial morphology suggestive of altered inner membrane permeability and swelling. This represented the first report of a retroviral gene product targeted to mitochondria, and suggested that p13(II)-induced alterations in the function of this organelle may play a role in HTLV-1 replication and/or pathogenesis. The more recent findings that both Vpr and Tat of HIV-1 are targeted to mitochondria reinforces the proposed relevance of mitochondrial metabolism to the life cycle of retroviruses. Thus, p13(II), Vpr, and Tat can be added to the growing list of mitochondrial proteins produced by clinically important human viruses, including Epstein-Barr virus, human cytomegalovirus, and hepatitis B virus. Mitochondria are known to play a critical role by providing an amplification loop required for the execution of signaling pathways leading to programmed cell death. The functional consequences of the interactions between viral proteins and mitochondria described so far have been attributed to either the positive or negative control of apoptotic responses mediated by this organelle. Further analysis of the effects of p13(II) on mitochondrial function is likely to add to our understanding of the mechanisms underlying the development of HTLV-1-associated diseases.
除了必需的调节蛋白Rex和Tax外，HTLV-1基因组还编码几种功能尚未明确的辅助蛋白。其中一种名为p13(II)的“孤儿”蛋白最近被证明可选择性地定位于线粒体，并诱导线粒体形态发生特定变化，提示内膜通透性改变和肿胀。这是关于逆转录病毒基因产物定位于线粒体的首次报道，并表明p13(II)诱导的该细胞器功能改变可能在HTLV-1复制和/或发病机制中起作用。最近发现HIV-1的Vpr和Tat都定位于线粒体，这进一步强化了线粒体代谢与逆转录病毒生命周期相关性的观点。因此，p13(II)、Vpr和Tat可以添加到由临床上重要的人类病毒产生的线粒体蛋白不断增加的列表中，这些病毒包括爱泼斯坦-巴尔病毒、人类巨细胞病毒和乙型肝炎病毒。已知线粒体通过提供执行导致程序性细胞死亡的信号通路所需的放大环发挥关键作用。到目前为止所描述的病毒蛋白与线粒体之间相互作用的功能后果，要么归因于该细胞器介导的凋亡反应的正调控，要么归因于负调控。对p13(II)对线粒体功能影响的进一步分析可能会增进我们对HTLV-1相关疾病发病机制的理解。
