Maelfait team: Nucleic Acid Immunity lab

Research Field: Nucleic Acid Sensing in Antiviral Immunity

Team leader: Dr. Jonathan Maelfait

Tel: +32 9 33 13 710 - Fax: +32 9 221 76 73

Research topic

Our lab studies the interplay between viruses and the immune system. Our research contributes to the development of better vaccines and aims to understand the molecular basis of autoimmune disease.

Viruses are obligate intracellular pathogens and in order to replicate they need to deliver their RNA and DNA genomes inside the host cell. The cells that make up our body contain sensory molecules called nucleic acid receptors which detect virally derived nucleic acids. Different types of nucleic acid receptors activate distinct antiviral defence mechanisms which cooperate to clear the viral pathogen. Some receptors respond to infection by releasing antiviral molecules, which alert surrounding cells of the ensuing viral attack. Others instruct the infected cell to commit suicide thereby preventing viral dissemination.

Our research focuses on the identification of the precise molecular signatures that activate nucleic acid receptors and how viruses fight back by blocking the molecular signalling pathways that are activated upon infection.

In another aspect of our research we try to understand how nucleic acid receptors specifically recognise viral nucleic acids and avoid contact with cellular RNA and DNA. Healthy uninfected cells are packed with endogenous RNA and DNA molecules which are important for normal cell function. Unwanted detection of these nucleic acids can result in detrimental immune responses, including the development of autoimmunity.

Areas of expertise

  • Nucleic acid sensors
  • Innate antiviral immunity
  • Z-form nucleic acids and their interaction with ZBP1 and ADAR1
  • Methods to study protein-nucleic acid interactions, including CLIP-Seq

Technology transfer potential

  • Vaccine development
  • Antivirals

Recent publications

  1. Maelfait J. et al. Sensing of viral and endogenous Z-RNA by ZBP1/DAI induces necroptosis.
    EMBO J. 36, 2529-2543, 2017.
  2. Maelfait J. et al. Restriction by SAMHD1 Limits cGAS/STING-Dependent Innate and Adaptive Immune Responses to HIV-1.
    Cell Rep. 16, 1492-501, 2016.
  3. Maelfait J. et al. A20 Deficiency in Lung Epithelial Cells Protects against Influenza A Virus Infection.
    PLoS Pathog. 12, e1005410, 2016.
  4. Bridgeman A. et al. Viruses transfer the antiviral second messenger cGAMP between cells.
    Science. 349, 1228-32, 2015.
  5. Maelfait J. Stimulation of Toll-like receptor 3 and 4 induces interleukin-1beta maturation by caspase-8.
    J Exp Med. 205, 1967-73, 2008.

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