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 virus and the Human Immunodeficiency Virus type 1 (HIV-1), 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. For instance, HIV-1 DNA accumulation is potently inhibited by interferon-induced and unknown factors.
Our lab, named Interferon and antiviral restriction, which has been established recently 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, powerful, whole-genome CRISPR/Cas9 screens) and at characterizing the molecular mechanisms involved in their antiviral activity.
Our main projects are the following:
Key words
Interferon, antiviral restriction, HIV-1, influenza A virus, innate immunity, signalling, genetic screens
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. For instance, HIV-1 DNA accumulation is potently inhibited by interferon-induced and unknown factors.
Our lab, named Interferon and antiviral restriction, which has been established recently 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, powerful, whole-genome CRISPR/Cas9 screens) and at characterizing the molecular mechanisms involved in their antiviral activity.
Our main projects are the following:
- Understanding the antiviral activity of MX proteins against their viral targets
- Physiological role and potential involvement in innate immune signalling of MX proteins
- Identification and characterization of new interferon-induced, antiviral effectors against HIV-1 and influenza A virus and other human pathogenic viruses
Key words
Interferon, antiviral restriction, HIV-1, influenza A virus, innate immunity, signalling, genetic screens