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Published on: March 1, 2019
Mechanisms of viral entry: sneaking in the front door
Jennifer A Thorley1, Jane A McKeating, Joshua Zachary Rappoport
1School of Biosciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham, UK.
Abstract:
Recent developments in methods to study virus internalisation are providing clearer insights into mechanisms used by viruses to enter host cells. The use of dominant negative constructs, specific inhibitory drugs and RNAi to selectively prevent entry through particular pathways has provided evidence for the clathrin-mediated entry of hepatitis C virus (HCV) as well as the caveolar entry of Simian Virus 40. Moreover, the ability to image and track fluorescent-labelled virus particles in real-time has begun to challenge the classical plasma membrane entry mechanisms described for poliovirus and human immunodeficiency virus. This review will cover both well-documented entry mechanisms as well as more recent discoveries in the entry pathways of enveloped and non-enveloped viruses. This will include viruses which enter the cytosol directly at the plasma membrane and those which enter via endocytosis and traversal of internal membrane barrier(s). Recent developments in imaging and inhibition of entry pathways have provided insights into the ill-defined entry mechanism of HCV, bringing it to the forefront of viral entry research. Finally, as high-affinity receptors often define viral internalisation pathways, and tropism in vivo, host membrane proteins to which viral particles specifically bind will be discussed throughout.
Insights
New imaging and inhibition methods reveal diverse virus entry pathways into host cells. This research clarifies mechanisms for hepatitis C virus and other viruses, challenging older models.
Area of Science:
- Virology
- Cell Biology
- Molecular Biology
Background:
- Viruses utilize specific mechanisms to enter host cells, which are crucial for infection.
- Understanding these entry pathways is key to developing antiviral strategies.
Purpose of the Study:
- To review recent advancements in studying viral entry mechanisms.
- To discuss both established and emerging pathways for virus internalization.
- To highlight the role of host cell receptors in viral tropism.
Main Methods:
- Utilizing dominant negative constructs, inhibitory drugs, and RNA interference (RNAi) to block specific entry routes.
- Employing real-time imaging and tracking of fluorescently labeled virus particles.
- Analyzing host membrane proteins involved in viral binding and entry.
Main Results:
- Evidence supports clathrin-mediated entry for hepatitis C virus (HCV) and caveolar entry for Simian Virus 40.
- Real-time imaging challenges classical plasma membrane entry models for viruses like poliovirus and HIV.
- Insights into HCV entry pathways are advancing rapidly, positioning it as a key research area.
Conclusions:
- Viral entry pathways are diverse, involving direct plasma membrane penetration or endocytosis.
- Host cell receptors play a critical role in determining viral tropism and entry mechanisms.
- Advanced imaging and inhibition techniques are crucial for elucidating complex viral entry processes.
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