Human neurotropic polyomavirus, JC virus, agnoprotein targets mitochondrion and modulates its functions.

Human neurotropic polyomavirus, JC virus, agnoprotein targets mitochondrion and modulates its functions.
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DOI:
10.1016/j.virol.2020.11.004
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发表时间:
2021-01-15
期刊:
影响因子:
3.7
通讯作者:
Safak M
Safak M
中科院分区:
医学3区
文献类型:
--
作者:
Saxena R;Saribas S;Jadiya P;Tomar D;Kaminski R;Elrod JW;Safak M

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JC病毒编码一种重要的调节蛋白,称为Agnotein(Agno)。我们最近报道了Agno与其细胞伙伴的第一个蛋白质相互作用组,揭示了它针对各种细胞网络和细胞器,包括线粒体。在这里,我们报告了它的线粒体靶向的功能后果的进一步表征,并证明了它与线粒体网络和线粒体外膜的共同定位。AgNO的线粒体靶向序列(MTS)及其二聚化结构域在靶向中起着重要作用。数据还显示,AgNO阳性细胞的各种线粒体功能发生了变化,包括线粒体膜电位、呼吸频率和ATP产量显著降低。相反,线粒体的ROS生成和钙摄取也显著增加。最后,研究结果还显示,当Agno MTS被删除时,病毒复制显著减少,这突显了MTS在病毒生命周期中的AgNO功能中的作用。
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 Ca2+ 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.
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