Virus-host dynamics: how coronaviruses undermine cellular defence systems
Interview with Dr Silvio Steiner
What was the aim of your doctoral thesis?
Its original aim was to gain a better understanding of the role of stress granules* (SGs) in the context of antiviral cell defence. Many viruses block the development of SGs during an infection, so it is speculated that they also play a role in cellular defence. My aim was to study these granules during a viral infection and to investigate if and how they differ from other stress situations.
Many viruses block the development of SGs during an infection, so it is speculated that they also play a role in cellular defence. To understand the possible functions of SGs during a viral infection, I investigated their protein composition.
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The start of the COVID-19 pandemic strongly influenced the aims of my doctoral thesis. As a research laboratory that specialised in coronavirus research even before the pandemic, we focused our research priorities at the time entirely on SARS-CoV-2. As a consequence, my work with SGs took a back seat and my thesis split into two parts with different themes.
Given the urgency of the situation, a high priority was to learn as much as possible about the properties of SARS-CoV-2 in order to fight it more effectively. Our team focused especially on virus-host dynamics: for example, how temperature differences between the upper and lower respiratory tract affect SARS-CoV-2 in contrast to SARS-CoV. We also investigated how human lung cells react to the virus over the course of an infection. In addition, we studied the functions of different viral proteins of SARS-CoV-2 to understand more clearly how the virus manipulates our cells.
Temperature differences between the upper and lower respiratory tract affect reproduction of the SARS-CoV-2 virus. At the lower temperature of the upper respiratory tract, the virus is able to multiply better in human respiratory epithelial cells and defences against the virus are slowed down.
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What are the main findings of your dissertation?
Using the model coronavirus murine hepatitis virus (MHV)** as an example, I characterised the composition of SGs during an ongoing infection and compared it with that of SGs triggered by a chemical stress signal. My findings indicate that SGs triggered by MHV infection have a greatly altered composition compared to chemically induced SGs and no longer fit the classical picture of SGs.
For our studies of SARS-CoV-2 in the group led by Prof. Dr Volker Thiel, we used human lung cells to analyse differences between SARS-CoV-2 and its predecessor (SARS-CoV). For example, our team discovered that SARS-CoV-2 replicates better at the lower temperatures in the upper respiratory tract. This probably contributed to the much faster spread of SARS-CoV-2 compared to SARS-CoV. We also looked at what happens in the lung cells during infection and which cellular responses are induced.
To what extent will your findings help to advance research?
My findings contribute to our understanding of how human cells deal with certain stress situations and how these functions may potentially be infiltrated by viruses.
Our research into SARS-CoV-2 expands our understanding of the virus and its influence on the human body, helping to fight the virus more effectively. Our results lay a foundation we can build on. Another special project was writing a review article for a scientific journal. We summarised the literature on the life cycle of coronaviruses, creating a resource to help other scientists in their work.
What did you especially like about working on your thesis?
It was an incredibly exciting challenge to be at the centre of research in the early days of the SARS-CoV-2 pandemic and witness the latest findings live. Working directly with this new, unknown virus in a high-security laboratory was very exciting and I learned a lot.
In general, I enjoyed the variety involved in the work and the chance to help shape my project. I learned many new techniques and established some of them in our laboratory. I really liked the amazing team dynamic and the coordinated cooperation with other team members, especially during the difficult situation in the pandemic. Supervising Bachelor’s and Master’s students was a great experience too.
What projects do you have coming up, what are you going to do next?
I’ll be staying at the IVI in the group under Prof. Dr Volker Thiel, working mainly on characterising the function of a protein of SARS-CoV-2 called “NSP1”. This protein is able to suppress the defence mechanisms of human cells, making it easier for the virus to take over the cells.
After my exciting years in research, I’d like to go on to gain new experiences and see what it is like to work in the private or public sector.
Glossary
*Stress granules are tiny aggregates composed of proteins and RNA molecules that form in cells in response to stress, such as infection, temperature shock or food withdrawal. They help to protect the cell by stopping production of unnecessary proteins and focusing on damage repair. Stress granules can also be exploited by viruses to promote their own replication in the cell. Some viruses are able to inhibit or manipulate stress granulation in order to bypass the antiviral immune response and replicate themselves.
**Murine hepatitis virus (MHV) is a coronavirus that infects mice, causing liver disease. It is related to SARS-CoV-2, SARS-CoV and MERS-CoV and is often used in science as a model virus for the study of coronaviruses.
Last modification 27.04.2023
