Interview with Dr. Charlotte Uetrecht, Junior Research Group Leader at the Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Dynamics of Viral Structures Research Group
Within the scope of the VIRUSCAN project that is funded by the Horizon 2020 Research and Innovation Program of the European Union, Dr. Charlotte Uetrecht from Hamburg/Germany investigates individual viruses to be able to later identify them on a nanospring structure. MEDICA.de wanted to know: how does this work?
Dr. Uetrecht, first of all, what are the already existing virus identification methods?
Charlotte Uetrecht: On the one hand, we have the antibody-based diagnosis, which has been proven and tested for many years. In this case, virus-specific structures are identified through antibodies, a very sensitive approach – however, you already need to know the virus you are looking for. On the other hand is the so-called PCR, polymerase chain reaction, which has become a very common method. Here, the virus genome is cloned, though you also need to know what you are looking for. At the very least, you should know the virus family. Unfortunately, this method does not allow you to discern whether a virus is infectious or not. As long as the genome is present, it will be detected. This is exactly the aspect we hope to improve with the new system we aim to develop.
The VIRUSCAN project incorporates nanomechanics to allow virus detection. Could you please explain this approach?
Uetrecht: My contribution to this project is one portion of eight individual projects by various partners. Here in Germany or Hamburg, respectively, we are in charge of determining the mass of individual viruses in their different states. For instance, whether they are infectious or noninfectious. Meanwhile, our partners in the Netherlands are focused on the mechanics of viruses. We try to define what we are actually able to distinguish and what we can detect with nanosprings. Our colleagues in Spain advance the development of the actual nanospring.
Do viruses not occasionally resemble each other? How do you plan to tell them apart?
Uetrecht: We examine two parameters. What makes nanosprings so unique is that –in theory- you are also able to collect information about the structure of viruses. Many viruses differ fundamentally in their structure. For instance, the Ebola virus is very long, whereas Influenza is more rounded but also very large. In contrast, the norovirus is very small and round. That’s why there are different parameters as it pertains to mechanics and mass. Having said that, it’s certainly true that if you want to differentiate different noroviruses, for example, it gets more complicated because the values are more similar. In these cases, we need to examine whether we can achieve characteristic measurements under different conditions. This is one aspect we have to clarify.
Which viruses and how many viruses do you plan to examine first?
Uetrecht: We cover a relatively broad spectrum of human pathogens. This includes HIV, hepatitis B and C, several herpesviruses, adenovirus, norovirus, papilloma, and polyomaviruses for example. However, we are also going to investigate new viruses such as Ebola or Lassa.
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So you are gradually creating a database that later serves to compare viruses that were detected using nanosprings?
Uetrecht: That’s right. We want to compare the results from the spring with those from the database. We will likely not get the same values since the measurements are somewhat different. However, the database still gives us an idea of what the differences should look like.
So in future application, you take blood from patients and isolate the virus to analyze it later on by using the spring?
Uetrecht: The plan is to separate the virus from the blood using microfluidic systems. It should then be converted into the gas phase using electrospray and deposited on the spring. You subsequently measure the vibrational pattern of the spring. This lets you determine the mass and mechanical properties. By subsequently comparing the results to the database, you can hopefully determine the type of virus the patient had and the quantity found in the blood.
What happens if a virus changes? Would this falsify the results?
Uetrecht: Even though viruses mutate, these are generally only minor, gradual changes that have comparatively little influence on the mass. Having said that, they could have a major impact on mechanics, especially if the changes are structural. In these cases, we hope to be able to detect with the nanospring that we are faced with something different and new. You subsequently would need to consider whether you conduct a PCR analysis of the isolate to see what exactly has changed. This is very exciting, for instance when it comes to new viruses in Africa. Having said that, at a hospital in Europe, you are more likely do deal with well-known viruses.
When do you hope to apply the results of your research?
Uetrecht: The project is scheduled to run five years. The aim is to have a usable prototype near the end of the project that was already tested in the hospital. Ideally, there should also be a portable version at that time which could be used for field diagnosis in Africa for instance.