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Published on: June 16, 2023
Involvement of p32 and microtubules in alteration of mitochondrial functions by rubella virus
1Institute of Virology, University of Leipzig, Johannisallee 30, Leipzig D-04103, Germany.
Abstract:
The interaction of the rubella virus (RV) capsid (C) protein and the mitochondrial p32 protein is believed to participate in virus replication. In this study, the physiological significance of the association of RV with mitochondria was investigated by silencing p32 through RNA interference. It was demonstrated that downregulation of p32 interferes with microtubule-directed redistribution of mitochondria in RV-infected cells. However, the association of the viral C protein with mitochondria was not affected. When cell lines either pretreated with respiratory chain inhibitors or cultivated under (mild) hypoxic conditions were infected with RV, viral replication was reduced in a time-dependent fashion. Additionally, RV infection induces increased activity of mitochondrial electron transport chain complex III, which was associated with an increase in the mitochondrial membrane potential. These effects are outstanding among the examples of mitochondrial alterations caused by viruses. In contrast to the preferential localization of p32 to the mitochondrial matrix in most cell lines, RV-permissive cell lines were characterized by an almost exclusive membrane association of p32. Conceivably, this contributes to p32 function(s) during RV replication. The data presented suggest that p32 fulfills an essential function for RV replication in directing trafficking of mitochondria near sites of viral replication to meet the energy demands of the virus.
Insights
Rubella virus (RV) replication depends on mitochondrial protein p32 to traffic mitochondria for energy. Silencing p32 disrupts this process, reducing viral replication and affecting mitochondrial function.
Area of Science:
- Virology
- Cell Biology
- Mitochondrial Biology
Background:
- The rubella virus (RV) capsid (C) protein interacts with mitochondrial p32, suggesting a role in viral replication.
- Mitochondria are increasingly recognized as key players in viral pathogenesis.
Purpose of the Study:
- To investigate the physiological significance of rubella virus association with mitochondria.
- To elucidate the role of mitochondrial protein p32 in rubella virus replication.
Main Methods:
- RNA interference was used to silence p32 expression in RV-infected cells.
- Mitochondrial redistribution, viral replication, and mitochondrial function (electron transport chain activity, membrane potential) were assessed.
- Cell lines were also subjected to respiratory chain inhibitors or hypoxia before RV infection.
Main Results:
- Downregulation of p32 interfered with microtubule-directed mitochondrial redistribution in RV-infected cells.
- Viral replication was reduced under conditions of respiratory chain inhibition and mild hypoxia.
- RV infection increased mitochondrial electron transport chain complex III activity and mitochondrial membrane potential.
- p32 localization shifted to the mitochondrial membrane in RV-permissive cell lines.
Conclusions:
- Mitochondrial protein p32 is essential for rubella virus replication, likely by facilitating mitochondrial trafficking to energy-demand sites.
- Rubella virus infection induces significant alterations in mitochondrial function, including enhanced electron transport chain activity.
- The specific localization of p32 to the mitochondrial membrane in permissive cells may be crucial for its role in supporting viral replication.
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