Researchers at the University of Virginia School of Medicine have discovered that the deadly ebola virus uses a “molecular fist” to punch its way out of vesicles – the secure pockets that cells keep captured viruses and other unwanted agents in until they can be disposed of.
Once it has punched its way out of the vesicle, the virus escapes into the fluid environment inside the cell – the cytoplasm – where it wreaks havoc by converting the cell machinery into a virus-replication factory.
The team behind the discovery, led by Lukas Tamm, professor of Molecular Physiology and Biological Physics at the University of Virginia School of Medicine, writes about it in the Journal of Virology.
The finding identifies an important target for blocking the infection process of a deadly pathogen for which there is currently no defense, and many fear may be used for bioterror.
The deadly, highly contagious virus is spreading in the African countries of Guinea, Liberia and Sierra Leone. In April 2014, the aid agency MSF said Guinea was facing an unprecedented outbreak of ebola.
Meanwhile, there are concerns that ebola will eventually spread around the world unless we find a way to stop it.
In their study, Prof. Tamm and colleagues found that after a cell captures an ebola virus, it imprisons it in a vesicle, awaiting elimination. But while it is the vesicle, the virus reacts to the pH (the amount of acidity) of the inside of the vesicle. The reaction causes a molecule on the surface of the virus – a glycoprotein – to form a “fist” that allows the virus to punch through the vesicle wall into the cell’s cytoplasm. Once the virus escapes into the cytoplasm, it goes about its work of converting the cell into a factory for making copies of itself.
Prof. Tamm says if ebola stayed in the vesicle, it would be harmless, the cell would simply digest it.
However, the virus escapes into the body of the cell, he adds, and “that’s when the danger happens. It does that by fusing its own membrane with that cellular vesicle membrane, and that lets the RNA of the virus out into the cell to replicate, to basically cause havoc in those cells.”
Prof. Tamm goes on to explain that it is somewhat ironic that when the virus first approaches the cell, the molecule that will eventually form the fist appears like an outstretched hand.
In order to clench the “hand” and form the fist, the virus needs to identify amino acids within itself. And that could be the key to blocking the virus: “If you lose those [amino acids],” Prof. Tamm explains, “it would always be in the extended hand formation.”
The team tested their findings by working with virus-like particles that behave like ebola but are safe to use in the lab. They confirmed the idea of the fist-clenching process, and verified it in test tubes and live cells.
They also created a computer model of the process, which has helped to further understand how ebola infection works.
The team hopes their work will not only greatly help scientists get a step closer to stopping ebola infection, but also do the same with other viruses that have similar fist-clenching structures, as Prof. Tamm explains:
“Once you have visualized the molecular shape changes that these structures undergo upon cell entry, you can see what molecules or potential anti-viral drugs could interfere with this process. You have these contacts that need to be made to make the clenching of the fist happen – if you could find a molecule that throws a wrench into the gears of that mechanism, you could actually block that from happening.”
In August 2013, Medical News Today reported how scientists discovered that the ebola virus assembles and reassembles like a “transformer.” Writing in the journal Cell, they describe how the same molecule that assembles and releases new viruses also rearranges itself into different shapes, with each shape controlling a different stage of the life cycle of the virus.