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13:04
A Protocol for Analyzing Hepatitis C Virus Replication
Published on: June 26, 2014
Hepatitis C virus RNA replication is regulated by Ras-Erk signalling
Sarah Gretton1, Mair Hughes, Mark Harris
1Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
The Journal of General Virology
|November 6, 2009
Summary
Hepatitis C virus NS5A protein impacts Ras-Erk signaling, crucial for viral RNA replication. Low-level Ras-Erk activity is needed, but complete inhibition hinders replication, suggesting NS5A regulates viral RNA levels.
Area of Science:
- Virology
- Molecular Biology
- Cellular Signaling
Background:
- Hepatitis C virus (HCV) NS5A protein partially inhibits Ras-Erk signaling via a C-terminal motif.
- The precise role of Ras-Erk signaling in the HCV life cycle is not fully understood.
Purpose of the Study:
- To investigate the role of Ras-Erk signaling in HCV RNA replication.
- To determine if MEK1 inhibition affects viral RNA levels.
Main Methods:
- Utilized genotype 1 and 2 transient luciferase subgenomic replicon systems.
- Employed pharmacological inhibitors (U0126, PD184352, PD98059) and genetic inhibition (dominant-negative MEK1) of MEK1.
Main Results:
- U0126 and PD184352 decreased HCV RNA replication.
- PD98059 showed a modest increase in replication, with no identified off-target effects.
- Dominant-negative MEK1 also reduced RNA replication, confirming inhibitor data.
Conclusions:
- A low level of Ras-Erk signaling is necessary for efficient HCV RNA replication.
- Complete inhibition of Ras-Erk signaling is detrimental to replication.
- HCV NS5A may modulate viral RNA replication by perturbing the Ras-Erk pathway.
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