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Immunopathology of Virus Infections

A systematic survey of P2Y receptors

Line’s PhD research is now published in EMBO! In this study, we systematically investigated the responses of human macrophages to extracellular nucleotides and revealed that adenine- and uridine-based nucleotides induce a specific and transient cytokine response through activating MAPK signaling pathway. We further categorized the nucleotide sensing P2Ys into two subgroups: P2Y1/2/6/11 that govern inflammatory responses via cytokine induction, and P2Y4/11/12/13/14 that directly induce antiviral responses.

Congratulations to Line, Yiqi, Chris, Lila, and all the collaborators involved in this study!

Read more in the EMBO paper:
Systematic P2Y receptor survey identifies P2Y11 as modulator of immune responses and virus replication in macrophages

Text by Yiqi, illustration by Line.

Identification of MDM2 as a regulator for SARS-CoV-2 uptake

We are excited to present our latest research publication! Building on our previous work (Stukalov et al., 2020, Nature), we investigated the impact of the genetic depletion of 21 host proteins on five different viruses. Our findings showed an increased SARS-CoV-2 replication in MDM2 knockout cells, which was virus-specific. This phenomenon can be attributed to the notable elevation of ACE2 levels in the absence of MDM2, thereby triggering an augmented SARS-CoV-2 uptake. Furthermore, our study highlights the crucial role of the MDM2 ubiquitination site Lysine 788 in stabilizing ACE2 and its significance in the context of SARS-CoV-2 particle uptake.

Congratulations to all the authors involved in this exciting research!

Read more here: MDM2 Influences ACE2 Stability and SARS-CoV-2 Uptake

Text and illustration by Quirin.

TRR353: Death Decisions funded!

We are excited that our collaborative research center Transregio “Cell death decisions” (TRR353) has been approved for funding. TRR353 focuses on innovative and groundbreaking research related to the regulation of cell death decisions. Together with our colleagues at the University of Konstanz and the Albert Ludwig University of Freiburg, we will study how, why and when cells decide to die and how this can be exploited for therapeutic purposes. This funding will allow us to study the regulatory mechanisms of oxeiptosis, and the relationship of oxpeiptosis to other cell death pathways.

We are hiring PhD students for this project soon, so keep your eyes open!

Text by Lara.

Targeting host 2’O-methyltransferases to suppress Influenza virus

We are proud to be part of the massive effort, spearheaded by Hiroki Kato and his team from Bonn, that revealed the critical role of the host RNA 2’O-methyltransferase MTr1 in influenza A/B cap-snatching! The activity of MTr1 is pivotal for Influenza A and B but not for other cap-snatching viruses and can be inhibited by a host-directed small molecule to achieve an antiviral effect through a novel mechanism.

Congratulations to Hiroki Kato in Bonn and collaborators for the fabulous manuscript published in Science!

Read more here: Inhibition of cellular RNA methyltransferase abrogates influenza virus capping and replication

Text by Valter and illustration by Andreas.

Bringing our research around the world!

As the world gradually recovers from the pandemic, we are also gradually resuming our physical conference attendance! Since the beginning of 2023, we have visited Ulm, Sitges (Spain), Paris (France), Snowbird (US), Gdansk (Poland), Crete (Greece), Würzburg, and certainly many more! Here’s what Innates have to tell about their experience:

Becoming a scientist involves learning to conduct science and socializing within the scientific community. Talking about current research and discussing future projects shaping the landscape of our research interests is vital for scientific progress. Therefore, I was thrilled to participate in the GfV, which allowed me to get to know top-notch virologists and comprehend Germany’s research interests. Although studies on SARS-CoV-2 were getting justified attention, I nevertheless felt that I was in good hands with my niche topic due to the size of the conference. For the first time, I had the opportunity to connect with scientists within my specialized field, enabling me to discuss this on a deeper level and understand how others are approaching similar goals.

On the other hand, broader and more international conferences, such as the 18th International Conference on Innate Immunity, gathered scientists from excellent research societies worldwide. It was a pleasure to be part of this gathering, hear talks about the discovery of novel signaling pathways, and meet the scientists behind it. All in all, attending conferences is just a win for you and your colleagues at home, who can profit from your reports and impressions.

I gave a talk about protein turnover in flu-infected cells at both conferences. GfV was my first-ever conference, and I fully enjoyed it! The atmosphere was really friendly, and I got to know many researchers with their interesting projects. A large number of students at the conference made it particularly easy to build connections. The conference had a lot of content, and I wish I had 10x the time to go through and absorb everything! Last but not least, it was great to meet our old colleagues Teresa and Pietro!

The 18th International Conference on Innate Immunity in Crete has a more relaxed and intimate setup with a more international group of scientists. It was an eye-opening conference and an excellent opportunity to hear about current trends in innate immunity! I learned a lot about different topics in innate immunity that we rarely touch in our lab and received many feedbacks and inspiration for my own projects. Besides, the food was amazing 😉

Cell Symposium: Viruses in health and disease (March 19–21, 2023, Sitges, Spain) was amazingly organized by Cell Press regarding novel insights on virus-microbiota interactions, SARS-CoV-2 structural biology and antiviral treatments, and emerging viruses. There, I presented our latest work focusing on the essential role of IKKα in the SARS-CoV-2 entry mechanism.

Additionally, I was selected to give a talk on this project at the French Days of the virology society (April 17-18, 2023, Paris, France). With the aim of developing Franco-German collaboration, our team joined great discussions at Pasteur Institute.

Thanks to Hao Wu, Russell E. Vance, and Andrea Ablasser for organizing the amazing Keystone conference “Innate Immunity: From Innate Sensing to Adaptive Responses” and giving us the opportunity to present our research. The time in Snowbird was an amazing opportunity to exchange with other researchers from all around the world.

It was a great pleasure to attend the 8th European Congress of Virology, taking place in Gdańsk, Poland, and organized by Prof. Thomas Mettenleiter from the Friedrich Loeffler Research Institute and Prof. Krystyna Bieńkowska-Szewczyk from the University of Gdańsk, where I did my studies. Returning to my hometown and reconnecting with the members of the lab that initially sparked my interest in virology, including my previous supervisor, Dr. Andrea Lipińska, alongside numerous current and former students, made the experience even more special. The conference brought together experts from a variety of subfields of virology and allowed me to appreciate unusual topics that I usually am not exposed to, such as the unusual split genomes strategy of multipartite plant viruses or the therapeutic potential of defective viral genomes of the flaviviruses.

I was selected to present my work at the 18th Innate Immunity Conference in Crete, Greece. This was a suitable theme for the future direction of my work, where I am focusing to explore the Innate specific proteins that are targeted by different variants of SARS-Cov-2. The major focus of this conference was inflammasomes and related pathways. I learned a lot about recent progress and directions in the cell death field and the NLRP protein family. Some topics were extremely interesting to me, like the “discovery of Panoptosis” and “Interferon exhaustion”. I received some valuable input from the researchers participating in this conference. There were good opportunities to connect with fellow researchers during coffee time, lunch, and dinner. The conference team also arranged a city tour, which was a fantastic experience. It was a great opportunity to connect with researchers gathering from different parts of the world and exchange ideas.

I had the opportunity to attend the Else-Kröner-Symposium in Würzburg. It was very interesting to see how results from basic immunology research were applied in clinical settings. To see the growing prevalence of translational approaches is promising and encouraging as it shows that our research has the potential to contribute to improving patients’ health in the future.

Where will we take our science next? Keep an eye on our homepage for future exciting updates!

Text and photos by the respective section authors.

Excellence initiative CiViA is funded!

Our colleagues from Aarhus University and us got funding for our joint excellence initiative Center for Immunology of Viral infections (CiViA). The Danish National Research Foundation will sponsor this initiative for up to 10 years!

In CiViA, we aim to discover novel antiviral mechanisms and unravel the decisive factors between protective and pathological immune responses. Moreover, besides providing spectacular infrastructure, we will team up with philosophers to prepare for the next paradigm shifts. We look forward to exciting times ahead!

Read more here:

Text by Andreas.

New host factors mediating SARS-CoV-2 entry and pathogenesis

This amazing study also reports repurposed ADAM inhibitors exerting antiviral activity against SARS-CoV-2 and its related variants of concern both in vitro and ex vivo. Such knowledge will help to develop new therapies to fight against COVID-19 as ADAM17 and ADAM10 expression correlates with disease severity in patients.

Congratulations to Vincent and Sabri, our collaborators from the Lichtenthaler’s lab and all authors!

Read more here: ADAM10 and ADAM17 promote SARS-CoV-2 cell entry and spike protein-mediated lung cell fusion

Text and illustration by Vincent.

Defining highly functional SARS-CoV-2-specific CD8+ T cells

We are finishing the year with an amazing collaborative work performed with Dirk Busch’s lab! In this study, we uncovered that SARS-CoV-2-specific CD8+ T cells are detectable up to 12 months post-infection. Moreover, by scRNA sequencing, we were able to develop cytotoxic engineered T cells allowing us to define cell signature for highly functional SARS-CoV-2-specific CD8+ T cells.

Congratulation to all the people involved in this great study!

Read more in the Cell Reports paper: Recruitment of highly cytotoxic CD8+ T cell receptors in mild SARS-CoV-2 infection

Discovery of a cellular degradation mechanism for viral PPP-RNA

We are excited to share that our manuscript was recently published in Nature Communications. You can now read about our work on the evolutionarily conserved class of Nudix hydrolases in the context of innate immunity.

We identified Nudix hydrolase 2 (NUDT2) as one key player to clear cells from viral triphosphorylated RNA (PPP-RNA). NUDT2 trims those RNAs into monophosphorylated RNA (P-RNA), which then serve as a substrate for the canonical XRN-1 degradation pathway.

This was a great collaborative effort, and we thank all our collaborators for their contributions. Congratulations to Bea, Karsten, Quirin, Line, Pietro, Sarah, and Andreas.

Read the whole story here: NUDT2 initiates viral RNA degradation by removal of 5′-phosphates

Analysis of evolutionary conserved viral nucleic acid binding proteins

We are very happy that our manuscript on evolutionary conserved viral nucleic acid binding proteins was published in Nature Communications.

It describes the most comprehensive evaluation of viral nucleic acid interactions in human, mouse and flies. We used conservation of binding properties over evolution to identify proteins that are relevant for innate immunity.

This was a great collaborative effort particularly between our laboratory and the laboratories of Jean-Luc Imler and Carine Meignin. Congratulations to Rike, Chris, Alexey, Line, Vincent, Teresa, Cathleen, Lila, Matthias & Andreas!    

Read more in the Nature Communications paper: Cross-species analysis of viral nucleic acid interacting proteins identifies TAOKs as innate immune regulators