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InnateLab

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InnateLab

Immunopathology of Virus Infections
Institute of Virology
TUM School of Medicine
Technical University of Munich

Category: newpaper

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Uncovering the importance of protein turnover regulation in IAV infection

Protein turnover is crucial to the cellular response to internal and external changes. In our publication in Cell Systems, we systematically profiled the protein turnover changes in cells infected by the influenza A virus (IAV). We identified more than a thousand virus-affected proteins with turnover changes (tVAPs) and demonstrated their important roles in IAV infection by intersecting them with published IAV interactome and genome-wide screens and performing additional functional analyses. We further investigated a splicing factor GPKOW, which we found to be an antiviral tVAP that modulates the host’s innate immune response. The data can be explored here: https://pulsechase.innatelab.org/

Congratulations to Yiqi, Chris, Philipp and Alexey – it was a successful collaboration across multiple generations of Innates!

Read more here: Protein turnover regulation is critical for influenza A virus infection

Text by Yiqi.

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mRNA therapy as a potential treatment against SARS-CoV-2

In our publication in EMBO reports, we investigated the effectiveness of LNP-formulated IFNλ1  mRNA (ETH47) in treating SARS-CoV-2 infection. ETH47 successfully induced an ISG response without excessive inflammation and inhibited SARS-CoV-2 replication in our in vitro and in vivo models. These promising results highlighted the possibility of using mRNA therapy in treating virus infections and laid the foundations for the upcoming clinical trials of ETH47.

Congratulations to Yiqi, Vince, and our collaborators from ETHRIS and Aarhus University!

Read more here: Mucosal IFNλ1 mRNA-based immunomodulation effectively reduces SARS-CoV-2 induced mortality in mice

Text by Yiqi.

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Multiomics analysis of the monkeypox virus

The recent outbreaks of the monkeypox virus (MPXV) raised concerns about the impact of poxviruses on public health. In our publication in Nature Communications, we present a comprehensive analysis of the transcriptomic, proteomic and phosphoproteomic changes induced by MPXV infection in primary cells. In addition to identifying virus-perturbed pathways, such as innate immunity and TGF-β signalling, we revealed dynamic phosphorylation of both host and virus proteins and uncovered the role of MPXV H5 phosphorylation in its function. Leveraging our omics data, we predicted and validated several drugs that inhibit MPXV replication. We hope our research will deepen the understanding of MPXV biology and facilitate the development of novel therapeutics against MPXV!

Congratulations to Yiqi, Valter, Vince, Quirin, Sabri, Karsten, Alex, and all the collaborators involved in this study!

Read more here: Multi-omics characterization of the monkeypox virus infection

Text by Yiqi.

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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.

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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.

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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.

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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.

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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

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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

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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

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Institute of Virology,
Immunopathology of viruses
Translatum (Bau 522), Room 22.1.31
Einsteinstr. 25, 81675 Munich

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Prof. Dr. Andreas Pichlmair
Immunopathology of Virus Infections Laboratory, Institute of Virology, Technical University of Munich
Einsteinstr. 25, D-81675 Munich, Germany
tel: +49 (0) 89 4140 9270, email: andreas.pichlmair@tum.de

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