Dr. Wyler, how can your recent publication on bulk and single-cell transcriptome profiling of SARS-CoV-2 infected cell lines impact the fight against the COVID-19 pandemic?
We do have an indication for a compound in the paper, an Hsp90 inhibitor. However, we see it primarily as a contribution to basic research into the molecular biology of the SARS-CoV-2 infection. A thorough knowledge of what happens in infected cells in a range of biological models in the end hopefully provides the basis to establish successful treatment options.
What further information does the single cell transcriptome of SARS-CoV-2 infected cell lines provide that bulk RNA-seq can’t deliver?
Virus infections are a very heterogeneous process. Already in a simple cell line model, the amount of virus particles entering the cells and the progression of infection can vary a lot. Methods averaging many cells such as bulk RNA-seq would mask these differences.
Why did you choose the cell lines that were used as infection models in your study?
Cell lines can be obtained in large amounts and can be easily perturbed both by genetic modifications, transfections or compounds. However, a complete picture obviously needs a range of models, particularly including more physiological ones like organoids or ex vivo infected tissues. And of course, all the data needs to be compared to what is observed in patients.
What difference can you see between SARS-CoV and SARS-CoV-2?
We have seen a stronger induction of the interferon response by SARS-CoV-2, which would lead to a stronger release of cytokines. COVID-19, the disease caused by the virus infection, is characterized by the entry of substantial amounts of immune cells into the lung, which eventually cause lung damage. These immune cells are attracted by cytokines, and thus this observation might be of clinical relevance.
What do we know about this latest virus and what distinguishes it from earlier types of coronavirus?
The new coronavirus is relatively closely related to other known coronaviruses, particularly to the “old” SARS virus known from 2002/2003. Decades of Coronavirus research are now key for the relatively fast progress in understanding the virus the disease. Comparisons to previously known human coronaviruses are at the moment still at the beginning, since the new SARS-CoV-2 is really special due to the combination of a lack of immunity within the population, and the fast and worldwide spread.
What were the most surprising or interesting aspects that were discovered in connection to the ongoing COVID-19 research that you have found so far?
The fast spread of the virus and how often very severe cases of the disease can occur are in my opinion the most important aspects, which also make it important that we work to achieve fast progress in understanding this pandemic.
What should be the priorities for basic infectious disease research in the current pandemic?
On one side, we need to thoroughly study the immunology of the infection in order to understand the varying susceptibility to the infection, and to establish a successful vaccine. On the other side, the molecular basics of the pathogenesis need to be studied in order to elucidate why some patients suffer from a severe form of the disease, whereas others are hardly symptomatic.
What methods are of particular importance to study virus-specific inflammatory response?
An important task will be to integrate and compare all the data that is coming in from different methods and different research groups worldwide. This mostly bioinformatic work is only at the beginning and will be of huge importance.
What are research aspects that should be supported by the European Commission or other funding body’s in the long term, to ensure the medical and scientific communities will be in a better position to respond to future outbreaks?
Funding for biomedical research is on a good way, particularly for projects going towards applied/clinical research. Social sciences and humanities also need to be put in a position to investigate the effects of the pandemic and how to cope with it. Still, basic research in all fields should not be neglected by shifting funds to SARS-CoV-2/COVID-19 projects. Coronavirus research was, for many years, not in the spotlight and better funding might have helped for the current situation. Likewise, we can only know to a certain degree what future challenges to expect. Underfunding research areas that are not “hot” at the moment would therefore be detrimental.
Read Emanuel Wylers most recent preprint on on bulk and single-cell transcriptome profiling of SARS-CoV-2 infected cell lines here. If you would like to learn more about the results obtained in this study have a look at Emanuels blog (in German only).
Interested in learning more about Emanuel Wylers recent preprint on on bulk and single-cell transcriptome profiling of SARS-CoV-2 infected cell lines, read our blog post on the topic here:
Or you can read our blog looking in depth at immunology research on the Nadia Instrument: