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

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

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

New paper on inflammasome activation by dsRNA published in Science!

Virus generated dsRNA directly binds to NLRP1 to activate the inflammasome. NLRP1 has a quite restricted expression pattern and therefore this type of inflammasome activation escaped the attention thus far. Through the use of our virus collection, we identified the activation of NLRP1 by the dsRNA producing virus Semliki forest virus. The paper just got online in Science, great stuff.

The article can be found here.

Our review on screening strategies is published in Viruses

Novel approaches and careful experimental design, combined with large-scale, high-throughput methods and cutting-edge analysis pipelines, have to be utilized to delineate the antiviral innate immune landscape at a global level. In this review, we describe different currently used screening approaches, how they contributed to our knowledge on virus–host interactions, and essential considerations that have to be taken into account when planning such experiments.

The review can be found here.

New Paper on cellular effects of persistent expression of viral nucleic acids

In this collaborative project, Chris and Hendrik found that long-term delivery of RIG-I ligand leads to cytostasis. Surprisingly, unlike found for other innate immune stimuli (e.g. LPS) persistent activation of the RIG-I pathway does not lead to tolerance. We hypothesize that this system recapitulates the situation in HCV-infected livers, which requires constant re-infection of cells in order to persistently propagate the virus. A beautiful story – which you can read here.

Christian Urban