Dr Vincent GRASS ( Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany)

Contact : Marlène Dreux

 

COVID-19 is a complex disease characterized by fulminant replication of SARS-CoV-2 and associated virusinduced comorbidities. Here, we performed genome-scale analyses combining interactome studies of SARS-CoV-2 along with transcriptome, proteome, ubiquitinome and phosphoproteome of infected cells, and as compared to SARS-CoV-1. Next, our multiple datasets were projected onto the global network of cellular interactions, enabling the identification of distinct and common hotspots that could be targeted by repurposed antiviral therapies. Notably, we further performed high-throughput inhibitor screens leading to identify host metalloproteases as newly-assigned proviral factors. Moreover, a CRISPR-based knock-out screen led to the characterization of ADAM17 as a facilitator of SARS-CoV-2 cell entry and ADAM10 as a host factor required for lung cell syncytia formation, a hallmark of COVID-19 pathology. Similar workflow was then used to i) repurpose antiviral drugs against both viral and host enzymes, thus to pharmaceutically block methylation of the viral RNA 2'-O-ribose cap, and ii) characterize unconventional host factors regulating endosomal maturation and SARS coronavirus entry.
Overall, combing genome-wide approaches with screening for drug repurposing led to the identification for new key host factors, and hereby novel antiviral compounds which exerted strong ex vivo activity at the nanomolar range.

Contact: Marc Vocanson

 

Sensory neurons in the skin have recently been shown to play important roles in the development of cutaneous inflammation. In this seminar, Dr. Kaplan will review current work in his laboratory demonstrating that pain-sensing neurons are sufficient to trigger Type-17 inflammation and defining the molecular pathways involved. In addition, work defining how different sensory neurons suppress inflammation by reprogramming mast cells to become hyporesponsive will be discussed.

Dr. Timothée BRUEL (Institut Pasteur - Unité Virus et Immunité)

Contact: Mathieu Mateo

 

Antibodies are produced by B cells as part of immune responses. They are polyfunctional molecules, recognizing foreign molecular motifs through their variable domains and interacting with immune cells via their constant region (Fc region). Our goal is to unravel the landscape of antiviral activities of antibodies and underlying mechanisms in the context of HIV-1 and SARS-CoV-2 infections.
Recombinant broadly neutralizing antibodies (bNAbs) targeting the HIV-1 envelope glycoprotein (Env) are promising molecules for therapeutic or prophylactic interventions. We have characterized their capacity to eliminate infected cells by NK-mediated antibody dependent cellular cytotoxicty (ADCC) and complement activation. We have also identified an additional antiviral activity of bNAbs, which block HIV-1 release by tethering viral particles at the surface of infected cells. In the context of SARS-CoV-2, we have developed a pipeline to isolate circulating viral strains and investigate their profile of neutralization by sera from convalescent and vaccinated individuals, as well as therapeutic antibodies. We also set-up assays to quantify ADCC of SARS-CoV-2 infected cells and used them to investigate the immune responses of asymptomatic individuals.
Overall, our projects aim at providing a basic understanding of antibody polyfunctionality and viral countermeasures, with implications for the development of the next generations of antibody-based vaccines and therapies.