Going Viral

Unpicking the mysteries of viruses


Viruses are one of the oldest and most pervasive components of the natural world. There are more of them on Earth than all bacteria, plant, and animal life combined, and they evolve faster than any living thing. Because of this diversity, treating viral infections and predicting their future evolution can be a challenge. But thanks to cutting-edge technology, scientists are unpicking the mysteries of these molecular machines, virus by virus; atom by atom.
Diamond is a hub for virus studies, attracting some of the leading researchers in the field. Diamond’s CRYSTAL beamline allows scientists to use synchrotron light to experiment on viruses under a higher level of containment than other life science beamlines at Diamond. Containment Level 3 means that scientists can study treatable pathogens that can be fatal to humans  in a safe and secure environment.
Thanks to these capabilities, scientists are able to scrutinise viral components in unprecedented detail. The knowledge they generate helps to identify drug targets and provides an insight into how viruses evolve – information that could help us to better manage outbreaks like the recent Ebola epidemic in West Africa.
Prof Jonathon Grimes is a Diamond Fellow and Professor of Structural Biology at the University of Oxford. He uses Diamond to study a variety of viruses, and is particularly interested in how they replicate. An integral component of the replication process, polymerases are enzymes made up of long strings of amino acids. They help to copy the viral genome and reproduce messenger RNA which is then used to reproduce the virus’s genetic code.
Dr Katherine McAuley demonstrates the sample handling cababilities on CRYSTAL (I03)
Using Diamond’s capabilities (MX beamlines and B21), Jon has successfully identified the structure of the polymerase involved in influenza C, a Containment Level 2 variety of flu which, together with influenza A and B,  infects approximately 3 to 5 million people every year, leading to between 250,000 to 500,000 deaths around the world. Understanding the atomic structure of the influenza C polymerase could be a major step forward in developing new treatments to fend off the spread of flu.
Jon explains: “Polymerases are just one component of the replication process, but if we can design compounds to stop it working, then it may be possible to develop a cocktail of drugs that together target different elements of the process and thus stop the virus in its tracks.”
The structural information Jon has uncovered may now be used to develop pharmaceuticals that target the influenza C polymerase and counteract viral replication. His findings could also provide insight into polymerases of other viruses in the same family, including the more aggressive and dangerous influenza A and B types. Meanwhile, Jon is now using Diamond to study the polymerases for rabies and Ebola, in an attempt to determine their structure and open up new avenues for the treatment of these diseases.
Shutting down the replication process is one way of combatting viruses, but another approach involves purposefully replicating the virus in a non-virulent form to act as a vaccine. Professor Dave Stuart is Director of Life Sciences at Diamond and Professor of Structural Biology at Oxford. His group is using Diamond to develop novel vaccines for viruses like foot-and-mouth disease and polio by mimicking the atomic structure of the virus shells.
All viruses contain RNA, and it is a genome, often made from RNA, that allows viruses to replicate and spread. Most vaccines use an attenuated version of a virus to build up the body’s immunity, so that when exposed to the actual virus, the immune system will recognise it and be able to defend against it.
However this approach requires high containment production facilities and is not always effective – the attenuated vaccines can themselves sometimes produce infection, and they are difficult to transport and store, particularly in hot climates.
Dave’s group are looking to create ‘empty’ virus shells that mimic the atomic structure of viruses but contain no RNA. Exposing the immune system to these empty shells would produce a response and induce immunity to the virus without any risk of infection. The group have already successfully produced a potential ‘empty’ vaccine for foot-and-mouth disease, which is currently being trialled in livestock in South Africa, and are now looking to develop the approach to work against polio.
Whilst Dave’s research focusses on specific viruses, his findings are also contributing to our wider understanding of viruses as a whole. There’s a lot of variety when it comes to viruses. They’ve been around for many millions of years, so they’ve had a fairly long time to adapt and evolve. But whilst viruses differ in terms of their structure, effect, and components, just like other species they can be grouped into families based on shared characteristics.
When it comes to viruses, understanding the bigger picture is vital. Dave observes: “Knowing the structure of viruses and viral elements is pivotal to combatting particular infections, but that knowledge can also help us to predict the structure and treatment options for other diseases.
We can study how the structure changes between different viruses and virus families, and as we build up that wider understanding, we become better equipped to anticipate what to expect, so that when we come to look at tackling another virus, be it an existing pathogen or something entirely new, we already have a base level of understanding which we can build on.”
Both Dave and Jon are at the forefront of efforts to track the evolution of viruses and the relationships between different families so that we can build up an evolutionary family tree. The team have solved the structure of many different viruses and virus components – some extremely ancient and some far newer. Their work is helping to shape our understanding of the viral world and providing us with the insight to respond to future outbreaks in a quick and effective way.
Exploring the atomic structure of viruses is key to developing more effective medical responses, both to existing pathogens and to those that may emerge in the future. Viruses are as varied as they are pervasive, but the work of scientists like Jon and Dave is helping to create a clearer picture of how they operate and evolve. And in this way, science will continue to make viruses a little less mysterious, and a lot easier to manage.

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