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

JC virus encodes an important regulatory protein, known as Agnopmtein (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.

Automated summary

The study reveals that the JC virus's regulatory protein Agno targets mitochondria and affects their functions. The mitochondrial targeting sequence (MTS) of Agno and its dimerization domain play crucial roles in this process. Furthermore, the study shows that Agno-positive cells exhibit reduced mitochondrial membrane potential, respiration rates, ATP production, as well as increased ROS production and Ca2+ uptake by the mitochondria.