Our projects

Interferon is produced by infected cells following the detection of pathogenic viruses and bacteria and is the first line of defence against infection. Interferon induces the expression of several hundred genes, names interferon-stimulated genes (ISGs) both in infected and neighbouring cells. The products of the ISGs, in turn, allow the establishment of a so-called antiviral state, which is able to prevent, or at least limit, viral replication. Most viruses, including influenza A and B viruses and SARS-CoV-2, are highly sensitive to this antiviral state and unable to replicate efficiently in cells that have been pre-exposed to IFN.

The dynamin-like, high-molecular weight GTPases MX1 and MX2 play a significant role in the interferon-induced inhibition of viral replication. Human MX1 is a restriction factor of broad antiviral activity, able to inhibit a great diversity of RNA and DNA viruses at different stages of their life cycles. The activity of MX2 seems narrower and has so far been restricted to HIV-1 and some primate lentiviruses. MX2 prevents HIV-1 DNA nuclear import and integration. Both MX1 and MX2 seem to recognize and interact with key components of viral nucleoprotein complexes to prevent viral replication, however their detailed mechanisms of action remain to be understood. Other antiviral ISGs inhibiting HIV-1 and influenza A virus have been identified, however, our preliminary data show that additional genes remain to be identified. We have recently identified the short isoform of NCOA7 (NCOA7-AS), which is interferon-inducible, as a new antiviral factor preventing endocytosis-meditaed viral entry.

Our lab, named Interferon and antiviral restriction, which has been established in January 2015 at the CNRS institute of research on infection of Montpellier (IRIM, ex-CPBS), aims at identifying new cellular effectors of the antiviral state (using, among other approaches, whole-genome scale CRISPR screens) and at characterizing the molecular mechanisms involved in their antiviral activity.

Our main projects are the following:

  • Understanding the antiviral activity of MX, NCOA7-AS, DDX42 and RER1 proteins
  • Physiological role and potential involvement in innate immune signalling of MX proteins
  • Identification and characterization of new interferon-induced, antiviral effectors against influenza A and B viruses and other human pathogenic respiratory viruses, including SARS-CoV-2 and RSV
  • Identification of new genes regulating respiratory virus replication in primary airway epithelia, and search for new antiviral compounds

Since March 2020, we’ve also been studying SARS-CoV-2: we’re chacterizing the inhibitory effect of interferons, identifying cellular regulators of replication through whole-genome CRISPR screens and screening molecules to help identify new therapeutical avenues.

Key words
Interferon, antiviral restriction, influenza virus, SARS-CoV-2, RSV, innate immunity, signalling, genetic screens, CRISPR, primary airway epithelia cultured at the air-liquid interface

Team leader

Caroline Goujon

INSERM tenure researcher (DR2)
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At a glance

The interferon-induced antiviral state strongly inhibits viral replication in human cells, which means that our cells are capable of expressing powerful, natural antiviral inhibitors. Our team aims at understanding the mechanisms of the interferon-induced antiviral defences. Using powerful approaches (such as whole-genome CRISPR/Cas9 knock-out functional genetic screens), we aim at identifying new interferon-induced effectors, and then at characterizing their antiviral activity.

Funding

Past funding:

   

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