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.

Now available: SARS-CoV-2 testing platforms

Incucyte S3 live-cell imaging screening paltform

We recently established a screening platform based on an incucyte S3 time-lapse microscopy system to test for antiviral drugs in BSL3 conditions. This allows us medium throughput testing (~72 compounds in 2-3 days) of antiviral compounds.

We are using  SARS-CoV-2 GFP  just published by our collaborator Volker Thiel, which serves as a great tool to study the influence of drugs in a time-resolved manner.

We want to thank for generous support from the Max-von-Bauernfeind Association and TUM!

10x Genomics - single-cell genomics in BSL-3 conditions

We recently installed a 10X single-cell sorter in our BSL3. Together with Herbert Schiller (Center of pulmonary diseases, Helmholtz) and other colleagues we are exploring new scientific avenues.

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