FOIL-VII at Raitenhaslach

We are just back from our seventh FOIL – Future Of Innate Lab – retreat at Raitenhaslach!

During the days we had heated (as expected in summer) discussions about not only our own projects but also the state of the art in various fields of our interest. It offered us a great overview of things going on inside and outside of our lab. Together we identified goals for individuals and the lab as a whole. We can’t wait to incorporate the new ideas and technologies in the upcoming year!

We concluded each day with a number of soft skill training. We improved our concentration at the Innate Pool Tournament and built some physical strength at the Innate Olympics (swimming, beach volleyball, Speedminton, long jump). Our creativity was further boosted by an intense dance workshop and an improvised Innate Band by the beautiful Wöhrsee.

We returned home with sores in our bodies, inspiration in our minds and joy in our hearts! Refreshed, we look forward to the future opportunities and challenges to fight virus infection!

Text by Yiqi. Photos by Andreas, Antonio, Anqi, Dorsa, Jyoti, Lila, Susanne and Virginie.

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

Therapeutic potential of ACE2-IgG4-Fc fusion protein against SARS coronaviruses

In collaboration with Ulla Protzer’s and Johannes Buchner’s lab, without forgetting the engineering skills of Formycon AG, we set up and characterized how ACE2-IgG4-Fc fusion protein could provide us new therapeutic tools in our non-stopping fight against COVID-19. While this construct can neutralize all SARS coronaviruses, including its variants of concern, it also has an activity at the picomolar range.

Congratulation to all the people involved in this great study!

Read more in the Antiviral Research paper: Picomolar inhibition of SARS-CoV-2 variants of concern by an engineered ACE2-IgG4-Fc fusion protein

Mechanism of transcriptional modulation by NS1 of Respiratory Syncytial Virus (RSV)

In a joint collaborative battle, Daisy Leung published a mechanism employed by NS1 of Respiratory Syncytial Virus (RSV) to modulate gene transcription: We (Valter/Philipp/Andreas) identified that NS1 binds to the mediator complex, an essential component of inducible gene expression. Jingjing and Daisy could show that NS1 thereby blunts the expression of genes associated with innate immunity.

Congratulations particularly to Jingjing, Nina, Jacqueline and Daisy, well done!

Read more in the Cell Reports paper: Nuclear-localized human respiratory syncytial virus NS1 protein modulates host gene transcription

HCMV infection induces citrullination to evade the antiviral defence

Gloria Griffante and colleagues (Santo Landolfo laboratory, University of Turin, Italy) discovered that HCMV infection induced protein citrullination, a post-translational modification catalyzed by PADs. In particular, the host defense protein IFIT1 was citrullinated by PAD2 and treatment with the enzyme impaired its ability to bind 5’PPP-RNA, thus constituting a novel immune evasion strategy. We contributed with mass-spectrometry and RNA-protein binding assays to characterize IFIT1 citrullination sites and PAD2-dependant modulation of its interaction with RNA.

Congratulations for this great work!

Read more in the Nature paper: Human cytomegalovirus-induced host protein citrullination is crucial for viral replication

New role of ZC3HAV1/ZAP in protection against HCMV

Using transcriptomics, proteomics and functional analyses, Ana Cristina Gonzalez-Perez from Melanie Brinkmann’s laboratory (Helmholtz Centre for Infection Research, Braunschweig) illuminated the novel antiviral role of ZAP in decelerating HCMV infections by specifically targeting viral UL4/5 transcripts. To highlight the antiviral effect of ZAP on the proteome level, we (Chris/Andreas) contributed time-resolved mass spectrometry profiling of HCMV-infected HHF-1 cells.

Congratulations to Cristina and all the people involved – fantastic work!

Read the full story in the mBio article: The Zinc Finger Antiviral Portein ZAP Restricts Human Cytomegalovirus and Selectively Binds and Destablizes Viral UL4/UL5 Transcripts

New cGAS receptors and signalling identified in flies

Fantastic discovery by the Rune Hartmann (Aarhus) and Jean-Luc Imler (Strassbourg) Laboratories now published in Nature! They have found the two new cGAS-like receptors that generate cyclic dinucleotides. These signalling molecules activate a STING-dependent pathway and contribute to antiviral immunity in flies. Our team (Line/Karin/Andreas) have contributed mass spectrometry experiments that helped to better characterize this novel pathway. 

Great Work! Big Congrats!

Read more in the Nature paper: Two cGAS-like receptors induce antiviral immunity in Drosophila