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Novel virus entry mechanism could lead to new drugs against poxviruses
April 12, 2006Research published in the Proceedings of the National Academy of Sciences on 11 April describes how the Imperial College London team discovered the mechanism allowing Vaccinia virus to shed its outer lipid membrane and enter cells. The mechanism is unique in virology and paves the way for development of new antiviral drugs.
Many viruses, such as influenza, are surrounded by a single lipid membrane, or envelope, and to enter cells this membrane must be removed. Previously, all enveloped viruses were thought to shed their lipid membrane by fusion with a cell membrane which allows the virus core to be released into the cell.
In contrast, the extracellular form of Vaccinia virus has two lipid membranes, meaning a single fusion event will not release a naked virus core into the cell. The researchers found that interactions between polyanionic or negatively charged molecules on the cell surface and glycoproteins on the virus particle caused a non-fusogenic disruption of the virus outer envelope, allowing the poxvirus to enter the cell.
As well as discovering how the double membrane problem is solved, the researchers demonstrated that polyionic compounds can be used to treat poxvirus infections, even days after infection has started. Disrupting the outer membrane with polyanionic compounds exposes the virus, allowing antiviral antibodies to be more effective. The disruption of the outer membrane also limits the spread of the virus in the body.
Professor Geoffrey L. Smith FRS, from Imperial College London and a Wellcome Trust Principal Research Fellow, said: "This work has uncovered a completely novel biological process. It increases our understanding of how viruses can manipulate biological membranes and will help the development of new drugs against poxviruses, such as variola virus, the cause of smallpox."
Imperial College London
As well as discovering how the double membrane problem is solved, the researchers demonstrated that polyionic compounds can be used to treat poxvirus infections, even days after infection has started. Disrupting the outer membrane with polyanionic compounds exposes the virus, allowing antiviral antibodies to be more effective. The disruption of the outer membrane also limits the spread of the virus in the body.
Professor Geoffrey L. Smith FRS, from Imperial College London and a Wellcome Trust Principal Research Fellow, said: "This work has uncovered a completely novel biological process. It increases our understanding of how viruses can manipulate biological membranes and will help the development of new drugs against poxviruses, such as variola virus, the cause of smallpox."
Imperial College London
Lipid Membrane News and Current Lipid Membrane Events RSSCentury-old rule of chemistry overturned -- major implications for drug delivery
A new study by research chemists at the University of Warwick has challenged a century old rule of pharmacology that defined how quickly key chemicals can pass across cell walls.
Carnegie Mellon develops computer model to study cell membrane dynamics
A cell constantly remodels its fluid membranes to carry out critical tasks, such as recognizing other cells, getting nutrients or sorting proteins.
Fusion in the fast lane
Using fast digital imaging, scientists from the Max Planck Institute of Colloids and Interfaces in Potsdam, Germany, together with researchers from Collîge de France, have succeeded in developing two different protocols by which one can initiate the fusion process in a controlled manner and observe the subsequent fusion dynamics with a temporal resolution in the microsecond regime.
With record resolution and sensitivity, tool images how life organizes in a cell membrane
What's the difference between a lifeless sack of chemicals and a living cell? It's all in the way they're organized, according to Stanford biophysical chemist Steven Boxer.
Finnish Centre of Exellence in Virus Research
The Finnish Center of Excellence (CoE) in Virus Research was selected as a member of the National Centers of Excellence Program by the Academy of Finland for the years 2006-2011.
FSU research produces images of AIDS virus that may shape vaccine
As the world marks the 25th year since the first diagnosed case of AIDS, groundbreaking research by scientists at Florida State University has produced remarkable three-dimensional images of the virus and the protein spikes on its surface that allow it to bind and fuse with human immune cells.
Schepens scientists are first to discover angiogenesis switch inside blood vessel cells
Scientists at Schepens Eye Research Institute, an affiliate of Harvard Medical School, are the first to discover a switch inside blood vessel cells that controls angiogenesis (new blood vessel growth).
New Tools Developed for Studying Neurodegenerative Brain Disorders
Penn State researchers have created an elegantly simple model of an axon-the extension of a neuron that communicates with other neurons-and have used this model to reproduce a change in the axon's shape that is characteristic of neurodegenerative disorders such as Alzheimer's and Parkinson's diseases.
New 'self-exploding' microcapsules could take sting out of drug delivery
Belgian chemists have developed "self-exploding" microcapsules that could one day precisely release drugs and vaccines inside the human body weeks or even months after injection.
Beyond genes: Lipid helps cell wall protein fold into proper shape
A protein that provides a vital passage through a bacterium's outer cell wall will misfold and malfunction if that wall is built of the 'wrong' material, scientists at The University of Texas Medical School at Houston report in a finding that has long-term implications for understanding diseases caused by misfolded proteins such as cystic fibrosis, Alzheimer's disease, and mad cow disease.
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