Department of Neuroscience, Laboratory of Molecular Neurovirology, MERB-757, Lewis Katz School of Medicine at Temple University, 3500 N. Broad Street, Philadelphia, PA, 19140, USA.
Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, USA.
Virology. 2021 Jan 15;553:135-153. doi: 10.1016/j.virol.2020.11.004. Epub 2020 Nov 25.
JC virus encodes an important regulatory protein, known as Agnoprotein (Agno). We have recently reported Agno's first protein-interactome with its cellular partners revealing that it targets various cellular networks and organelles, including mitochondria. Here, we report further characterization of the functional consequences of its mitochondrial targeting and demonstrated its co-localization with the mitochondrial networks and with the mitochondrial outer membrane. The mitochondrial targeting sequence (MTS) of Agno and its dimerization domain together play major roles in this targeting. Data also showed alterations in various mitochondrial functions in Agno-positive cells; including a significant reduction in mitochondrial membrane potential, respiration rates and ATP production. In contrast, a substantial increase in ROS production and Ca uptake by the mitochondria were also observed. Finally, findings also revealed a significant decrease in viral replication when Agno MTS was deleted, highlighting a role for MTS in the function of Agno during the viral life cycle.
JC 病毒编码一种重要的调节蛋白，称为 Agnoprotein（Agno）。我们最近报道了 Agno 的第一个蛋白质相互作用组及其细胞伴侣，揭示了它靶向各种细胞网络和细胞器，包括线粒体。在这里，我们进一步报告了其线粒体靶向的功能后果的特征，并证明了它与线粒体网络和线粒体外膜的共定位。Agnoprotein 的线粒体靶向序列（MTS）及其二聚化结构域共同在这种靶向中起主要作用。数据还显示，在 Agno 阳性细胞中，各种线粒体功能发生改变；包括线粒体膜电位、呼吸速率和 ATP 产生的显著降低。相比之下，还观察到线粒体中 ROS 产生和 Ca 摄取的大量增加。最后，研究结果还揭示了当删除 Agno MTS 时病毒复制显著减少，这突出表明 MTS 在病毒生命周期中 Agno 功能中的作用。
