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Published on: November 19, 2010
Differential expression of cellular prion protein (PrPC) in mouse hepatitis virus induced neuroinflammation
Satavisha Ghosh1, Rishika Jana1, Soumen Jana1,2
1Department of Biological Sciences, Indian Institute of Science Education and Research, Kolkata, Mohanpur, 741246, India.
Abstract:
The cellular prion protein (PrPC) is an extracellular cell membrane protein. Due to its diversified roles, a definite role of PrPC has been difficult to establish. During viral infection, PrPC has been reported to play a pleiotropic role. Here, we have attempted to envision the function of PrPC in the neurotropic m-CoV-MHV-RSA59-induced model of neuroinflammation in C57BL/6 mice. A significant upregulation of PrPC at protein and mRNA levels was evident in infected mouse brains during the acute phase of neuroinflammation. Furthermore, investigation of the effect of MHV-RSA59 infection on PrPC expression in specific neuronal, microglial, and astrocytoma cell lines, revealed a differential expression of prion protein during neuroinflammation. Additionally, siRNA-mediated downregulation of prnp transcripts reduced the expression of viral antigen and viral infectivity in these cell lines. Cumulatively, our results suggest that PrPC expression significantly increases during acute MHV-RSA59 infection and that PrPC also assists in viral infectivity and viral replication.
Insights
Cellular prion protein (PrPC) increases during MHV-RSA59 neuroinflammation in mice. Downregulating PrPC reduced viral load, suggesting PrPC aids viral replication and infectivity.
Area of Science:
- Neuroscience
- Virology
- Cell Biology
Background:
- The cellular prion protein (PrPC) is an extracellular protein with diverse, yet not fully understood, roles.
- PrPC has been implicated in various biological processes, including viral infections, where it may play a pleiotropic role.
Purpose of the Study:
- To investigate the role of PrPC in neuroinflammation induced by the neurotropic mouse hepatitis virus (m-CoV-MHV-RSA59) in C57BL/6 mice.
- To determine the effect of MHV-RSA59 infection on PrPC expression in the brain and specific cell types.
Main Methods:
- Utilized a mouse model of MHV-RSA59-induced neuroinflammation.
- Assessed PrPC expression at protein and mRNA levels in infected mouse brains.
- Examined PrPC expression in neuronal, microglial, and astrocytoma cell lines upon MHV-RSA59 infection.
- Employed siRNA-mediated downregulation of prnp transcripts to assess its impact on viral components.
Main Results:
- Observed significant upregulation of PrPC at both protein and mRNA levels in infected mouse brains during acute neuroinflammation.
- Demonstrated differential expression of PrPC in neuronal, microglial, and astrocytoma cell lines following MHV-RSA59 infection.
- Showed that siRNA-mediated downregulation of prnp transcripts led to reduced viral antigen expression and infectivity.
Conclusions:
- PrPC expression is significantly elevated during acute MHV-RSA59 infection.
- PrPC appears to facilitate viral infectivity and replication in the context of MHV-RSA59-induced neuroinflammation.
