A fascinating time to be a virologist

Tuesday, 12 October 2021 18:20

"I have always been attracted to science from a medical point of view. The choice of virology was a combination of relevance to human health and the technical possibilities of that time - the genome of viruses was small enough to study," says Professor Hans-Georg Kraeusslich, explaining why he became a virologist. On Wednesday, October 6, he received the honorary degree of doctor honoris causa in medical science for his scientific achievements and his long-term collaboration with Charles University.

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When you say Charles University, what is the first thing that comes to your mind?

That it is a strong, internationally renowned university with a long history, which is a good partner of our University of Heidelberg. I also have many personal ties to Charles University - I am a visiting professor at the First Faculty of Medicine and am honoured to have regular lectures and discussions with students here. My lab has also hosted several Ph. D. students and postdocs from the Czech Republic, all of whom studied at Charles University. I tried to count them - there were about 10 of them - some of them came to my lab only for short internships lasting a few months, but at least five students had been with me for several years. One of my first Czech co-workers, for example, was the current Vice-Rector for Science, Professor Jan Konvalinka, in the 1990s. Vojtěch Žíla, whom I first met during one of my lectures in Prague a few years ago, is currently a postdoctoral fellow in my lab. I am also the Vice-Chairman of the International Advisory Board of Charles University, so I am in close and long-term contact with the university, and I also collaborate with the Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences and the University of Chemical Technology in Prague.

At the beginning of your scientific career, you came to the attention of the scientific community in a somewhat unconventional way - thanks to a review that in a way set the direction of future research. What led you to this?

I was studying viral proteases - the process by which a larger protein is processed to pieces to make the virus infectious - in picornaviruses, a group of viruses that cause polio and other diseases. I had worked before on a retroviral protease and it was clear that these enzymes could be excellent targets for a new class of antiviral drugs. My postdoctoral supervisor was asked to write a review on this class of viral enzymes and asked me to do it with him; I was young and energetic, and took it on – I really learned a lot myself during this task.

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Why did you choose virology as your professional focus?

Virology won me over during my medical studies in Munich. I attended several extra curricular seminars and one of them was about DNA and RNA tumour viruses, and that really interested me. I was also influenced by my father, who was a population geneticist and was involved in animal breeding. Molecular genetics and molecular biology were frequent topics at our dinner table. My father talked about these topics in a very engaging way and I found it very interesting. I was always attracted to science from a medical point of view, and I wanted to work in a field that involved human diseases.

I was headed for research on human pathogens from the perspective of molecular biology and molecular genetics. And in the 1970s, when I started as a medical student, only viral genomes were small enough to work with and to analyse and modify them. The genomes of other disease-causing organisms such as bacteria and fungi were too large, and at that time it was not technically possible to work with them.

So the choice of virology was a combination of relevance to human health and the technical possibilities of that time. And I'm very glad for that: virology has gradually interested me more and more - and still fascinates me - and I never wanted to do anything else in my professional career.

VS1 4253You are a respected scientist, but you don't have a Ph. D. Have you ever felt that was a disadvantage?

Never - although I wanted to get a Ph. D. after my medical studies. However, at that time, it was not possible in the German education system, when you had studied medicine. But my experimental studies were similar to a Ph. D. thesis in terms of length and techniques. The fact that I didn't get a Ph. D. never played a role in my professional career. But I appreciate today's honorary doctorate all the more.

Your work focuses on the process of virus maturation, where a non-infectious clump of proteins becomes a mature, fully functional, infectious, and potentially dangerous viral particle. If you had to highlight one research project that is special to you, what would it be?

Actually, I've been working on one major research question all along - and that is how viruses - specifically the human immunodeficiency virus (HIV) that causes AIDS - are made, how the different parts interact with each other to give rise to an infectious particle. Outside the cell, the virus is actually a dead particle, a mere clump of proteins. It is only infectious and dangerous when it interacts with a cell where it can multiply and spread to infect other cells.

Of course, the recent work is always most interesting - what we did 30 years ago may have been interesting and important, but it is long surpassed by newer studies - it is always the current questions that are most interesting to scientists (smiles). Our recent research is looking at how the genetic information of a virus gets into the cell nucleus without disrupting the nuclear membrane in infected cells. This is a project that Vojtěch Žíla has worked on and it was recently published in the scientific journal Cell.

What are the current questions that you are interested in and looking for answers to?

There are still many unanswered questions. For example, a virus can be in an inactive form in the host cell and we cannot target it with therapies. We still don't fully understand the process that controls whether a virus is active or not. As yet unknown factors play a role in the activation process. We also still do not know exactly how viral proteolytic enzymes become activated to let the virus mature. This may seem like a trivial question, but it is essential to make the virus infectious, and it is something that I personally would like to find out before I retire.

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During the ceremony, you mentioned in your thank-you speech the rather unusual first meeting with the Czech virologist Jan Svoboda. You also knew Antonín Holý personally. How do you remember them?

I met Jan Svoboda for the first time in 1981 at the Munich train station - I was a medical student at the time and I was working in the laboratory on the topic of retroviruses. My supervisor invited me to accompany him to the station to meet Jan Svoboda. I didn't understand why we didn't invite him to come and show him the laboratories, because the institute was only ten minutes from the station. He explained to me that Jan Svoboda was on his way from France to Prague and was not allowed to leave the train, so my first meeting with the already well-known virologist took place on the platform through the rolled-down window of the train. We have met many times since then and these have always been very inspiring and pleasant meetings. Later, he sent me some of his latest scientific studies to read and comment on, which was a great honour for me. I also met Antonín Holý several times at the Institute of Organic Chemistry and Biochemistry and we had many interesting discussions, but we were not as close as I was with Jan Svoboda.

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Since 2019, you are also Dean of the Faculty of Medicine at the University of Heidelberg. How would you describe it to Czech students?

It is a medical school that is very strongly oriented towards research. The unique environment of Heidelberg, where there are a number of top research institutes such as the EMBL (European Molecular Biology Laboratory), that contribute to this. With EMBL, we have tandem groups in the Molecular Medicine Partnership Unit, where we combine clinically-oriented researchers at the university and basic scientists from EMBL. This is mutually beneficial because the clinicians get a stronger scientific background and, in turn, the basic researchers get in close contact with clinical practice.

Our main research areas at the Medical Faculty include oncology, cardiovascular diseases, neurosciences - especially neuro-oncology and neuropsychiatry, but also infectious disease research. In addition, there are many other fields where we achieve top results. The University of Heidelberg, which was founded in 1386 and is therefore only 38 years younger, is in many ways similar to Charles University - in research orientation, in size and in the number of specializations it offers.

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What is your advice for students who would like to pursue science?

Follow what you really enjoy and don't look at whether it will be popular in the future or a safe choice in terms of the job market - the world is always changing. Keep trying different things and don't stay in one place. It's more beneficial for the lab to keep Ph. D. students after graduation in the same place because they already know everything, but it's not optimal for a scientist´s development. One should be exposed to different environments where you learn something new in each one, and you can take the best of each lab in terms of how to do good science, as well as learning what you don't like and what you want to avoid. This will help you become a good scientist.

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The subject of the coronavirus is impossible to leave out: you have been one of the most important voices driving the anti-epidemic strategy throughout Germany over the last two years. You have tirelessly promoted testing and vaccination and have made a significant contribution to the fight against the disease in your clinic. From a purely scientific point of view, what fascinated or surprised you about the new coronavirus?

For a virologist specializing in human pathogens, the most interesting thing is to live and work in times of a pandemic - I never thought I would experience such a pandemic. It was fascinating to observe in real-time how the pandemic came about, how it spread, how we reacted, what we learned, what we did wrong, how it affects us as scientists as well as society as a whole. The pandemic has changed everything and we will see what has changed permanently and what will go back to the way it was. Some experts say the pandemic has changed the world for good, but I don't think so. When I walk through Prague and other cities now, I feel that life has already gone back to the way it was. The pandemic will always remain in our memories as a difficult and, for many people, as very sad time. But I do not expect that our behavior will change in the long term - although I'd like to be wrong.

From a scientist's point of view, it has been fascinating to watch the speed of vaccine development, but unfortunately antiviral research has not been able to keep up a similarly successful rate of progress. This needs to be improved As such, the SARS-CoV-2 virus is as interesting as any other pathogenic virus - you can't say that one is more interesting.

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What should we learn from the current pandemic and do you think we will be better prepared for any future pandemics?

We need to learn lessons and make plans for similar situations in the future. We must not allow the chaos that prevailed at the beginning of the pandemic to happen again. We should strengthen vaccine research and virus research in general, so that in the future we will be better able to respond to new viruses that we do not yet know. If, for example, we find a substance that works against all human and also some mouse and bat coronaviruses, such a substance would then be very likely to work against a new type of coronavirus as well. In Germany, we have made a strong push to support such research in preparation for future pandemics, and I would like to see more such activities at the European Union level.

At the same time, we should remember that there are other diseases than the coronavirus. For example, 700 000 people die every year from HIV, although thanks to Antonín Holý among others, we have excellent drugs. Many people die from tuberculosis, malaria, and other infectious diseases. In the last year, we have neglected prevention and early treatment of many diseases because health care has been significantly reduced to dealing with the coronavirus pandemic, and that is very unfortunate.

Is there anything else you would like to add in conclusion? 

I would like to wish Charles University to continue on the path it has started - it is an important member of the 4EU+ alliance, which brings together European research universities, and I believe that our collaborations will continue. I am a proud member of CU's International Advisory Board and hope to stay involved in the future development of CU.

Professor Hans-Georg Kraeusslich
Hans-Georg Kraeusslich is one of the most important European virologists. He studied medicine at the University of Munich obtaining a doctorate with Klaus von der Helm and, after completing his medical studies, spent a postdoctoral fellowship with the renowned American virologist Eckard Wimmer at the State University of New York at Stony Brook. Here he was involved in the seminal discovery of the regulatory mechanism of translation initiation in picornaviruses - a group of viruses that cause, among other things, polio. His career was largely devoted to studying HIV-1, where he made strong contributions to understanding viral replication and spread, to the development of antiviral drugs and to elucidating resistance mechanisms to drug therapy. Since 2019, he is Dean of the Faculty of Medicine at the University of Heidelberg.
Author: Pavla Hubálková
Photo: Vladimír Šigut, Shutterstock

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