Nucleic Acid Immunity lab

Maelfait Jonathan

Maelfait Jonathan

Research Teamleader
Group Leader VIB

Nucleic Acid Sensing in Infection and Inflammation


In order to replicate viruses need to deliver their genomes, which consist out of RNA or DNA, inside the host cell. Recognition of viral nucleic acids by immune receptors, called nucleic acid sensors, establishes a protective antiviral immune response. Some nucleic acid sensors respond to infection by releasing antiviral molecules such as type I/III interferons, which prepare surrounding cells for the ensuing viral attack. Others, including the nucleic acid sensor ZBP1, instruct the infected cell to commit suicide thereby preventing viral dissemination. Our research focuses on understanding the precise molecular mechanisms that activate nucleic acid sensors and how viruses fight back by blocking these processes.

In another aspect of our research we try to understand how nucleic acid sensors avoid activation by cellular RNA and DNA. Healthy uninfected cells are packed with RNA and DNA molecules, which make up our genetic material and contribute to normal cell function. Unwanted detection of these nucleic acids can result in the development of autoinflammatory diseases. We study the molecular processes that drive pathology through recognition of self-nucleic acids. In the future, this will enable us to selectively interfere with disease-causing mechanisms while leaving other cellular processes untouched.

Areas of Expertise

  • Nucleic acid sensors
  • Z-DNA/Z-RNA binding proteins (ADAR1, ZBP1)
  • Regulated cell death (apoptosis, necroptosis)
  • Type I IFN signalling

Technology Transfer Potential

  • Mouse models of autoinflammatory disease
  • Antiviral therapies

Selected publications

  • de Reuver, R. et al. ADAR1 prevents autoinflammation by suppressing spontaneous ZBP1 activation. Nature 607, 784-789 (2022). Visit ➚
  • Verdonck, S., Nemegeer, J., Vandenabeele, P. & Maelfait, J. Viral manipulation of host cell necroptosis and pyroptosis. Trends Microbiol 30, 593-605 (2022). Visit ➚
  • de Reuver, R. et al. ADAR1 interaction with Z-RNA promotes editing of endogenous double-stranded RNA and prevents MDA5-dependent immune activation. Cell Rep 36, 109500 (2021). Visit ➚
  • Devos, M. et al. Sensing of endogenous nucleic acids by ZBP1 induces keratinocyte necroptosis and skin inflammation. J Exp Med 217, e20191913 (2020). Visit ➚
  • Maelfait, J. et al. Sensing of viral and endogenous RNA by ZBP1/DAI induces necroptosis. EMBO J 36, 2529-2543 (2017) Visit ➚

Bibliography


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Haematoxylin and eosin (H&E; top) and immunofluorescent (bottom) sections from mouse skin showing normal (left panels) and thickened/inflamed (right panels) epidermis. Skin inflammation results from the spontaneous detection of self-nucleic acids by the nucleic acid sensor ZBP1 due to loss of function of two negative regulators ADAR1 and RIPK1 (see de Reuver, Verdonck et al. Nature 2022). Scale bars, 100 µm.