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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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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

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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

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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

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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

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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

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ISG20, a host nuclease that degrades HBV’s cccDNA

Together with our institute colleagues from the group of Ulrike Protzer and many other collaborating laboratories, we identified a new anti-HBV host factor, ISG20. This protein is induced upon interferon treatment and works in concert with APOBEC3 proteins to degrade HBV’s cccDNA in the nucleus of infected cells. By using affinity purification mass spectrometry, our laboratory (Chris/Andreas) confirmed the targeting of APOBEC3-modified cccDNA mimetics by ISG20.

Beautiful story and great work spearheaded by Daniela Stadler!

Read more in the EMBO Reports paper: Interferon-induced degradation of the persistent hepatitis B virus cccDNA form depends on ISG20

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Our multi-omics analysis of SARS-COV-2 and SARS-CoV – in Nature!

An example from our COVINET showing the regulation of PLAU upon infection, as well as its interaction with the ORF8 of CoV2.

We applied multi-omics data analysis to understand the interactions and impact of SARS-CoV-2 and SARS-CoV on the human proteome. In particular, we applied state of the art bioinformatics methods to precisely characterize what SARS-CoV-2 and SARS-CoV do to the proteome and provide links to potential molecular mechanism leading to COVID-19. Moreover, we established an integrated database (https://covinet.innatelab.org) that allows us to search for the effect of SARS-CoV-2 and SARS-CoV infection.

 

Congratulations to this tour de force to all involved people in our lab, particularly, Alexey, Virginie, Vincent, Valter, Chris, Darya and Yiqi as well as Ozge Karayel and Matthias Mann with whom we tightly collaborated. Moreover, we thank many other contributors who were instrumental to get this over the line! 

Please read our original manuscript published in Nature:

Multilevel proteomics reveals host perturbations by SARS-CoV-2 and SARS-CoV

Feel free to dive into the data at:

https://covinet.innatelab.org