science Archives - Page 2 of 4

December 6, 2021December 9, 2021

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

December 6, 2021December 6, 2021

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!

December 6, 2021December 6, 2021

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!

July 23, 2021December 6, 2021

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

July 23, 2021August 6, 2023

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

July 23, 2021December 6, 2021

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!

April 22, 2021August 6, 2023

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

December 1, 2020December 18, 2020

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.

November 18, 2020July 23, 2021

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.

June 23, 2020July 23, 2021

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.

InnateLab