An EOS project coordinated at the de Duve Institute

Virus: when the alarm sounds

UCLouvain press office

Prof. Thomas Michiels directs the Fundamental Virology Laboratory at the UCLouvain de Duve Institute. The EOS project he coordinates, launched in collaboration with teams from Ghent University, the University of Liège, and KU Leuven, aims to understand how viruses bypass immune defences. More specifically, researchers are interested in the interactions between viral RNA molecules and the innate response of the host.

Some viruses have a DNA genome and others have an RNA genome, but all viruses produce RNA molecules that can interfere with cell function and immune defence mechanisms. When a cell detects RNA, it infers a viral infection is present and triggers a defence programme to protect itself and neighbouring cells. But detecting a double-stranded RNA is extremely complicated, as normal cells also produce a small amount of double-stranded RNA. It’s absolutely essential that our cells not detect this endogenous RNA as the signal of a viral infection, otherwise they initiate an immune response that, if chronic, becomes catastrophic. For example, some people are constantly synthesising interferons, which causes serious developmental problems and mental retardation, and leads inevitably to premature death.

‘What interests us,’ Prof. Michiels explains, ‘is the mechanisms that “size up” cellular proteins in a way that ensures the detection threshold is not reached in normal cells yet makes it possible to detect a viral infection.’ The researchers identified an enzyme that destabilises the endogenous double-stranded gene in order to prevent the response from starting, and other sensors of this double-stranded RNA, including an enzyme that activates when the production of double-stranded RNA signals an infection.

One of the strengths of the collaboration is the diversity of viral models studied: flaviviruses, such as Zika or dengue (KU Leuven), Hepatitis E (Ghent University), influenza and respiratory syncytial viruses (Ghent University), and a notorious DNA virus that produces double-stranded RNA recognised by the immune system (University of Liège). UCLouvain researchers focus on picornaviruses, especially Theiler’s virus, a negative RNA virus that causes persistent infections of the nervous system. It has the distinction of persisting in spite of an immune response, and produces small proteins that interfere with the functioning of cells and the innate immune response. ‘We’re trying to see how Theiler’s virus interferes with the immune system, while knowing that the virus is acting on cellular components that play critical roles in regulating cell function’, Prof. Michiels says. ‘Viruses evolve rapidly, replicate very quickly and mutate very easily, to go where it hurts. By studying how a virus interferes with cell function, one often comes to understand certain elements of the functioning of the cell itself.’

Project: Viral interference with RNA sensing and processing

EOS, the Excellence Of Science: what researchers think

Budget flexibility
Prof. Michiels praises the EOS programme for its flexibility: ‘We can allocate budgets as and when the project unfolds, depending on the needs, whether human or material. It's revolutionary.’

Technical support
‘For most projects,’ Prof. Goosse (climatologist, UCLouvain) says, ‘climatologists do everything themselves, including developing models. Yet we need the technical support of computer scientists. This project allows us to focus on what we do best, physics, and benefit from the help of developers.’

Reasonable duration
Another convenience is funding duration. ‘Four years really allows you to focus on your work’, Prof Michiels says. ‘It’s what we lack most in fundamental research.’

International talent
Funding allows the recruitment of promising young researchers. For example, ten PhD students and five postdoctoral fellows from the world physics scene will join the project coordinated by Prof. Maltoni (physicist, UCLouvain).

Collaboration means better research
The resources available to researchers and the fact that this is a collaboration between several institutions with recognised expertise provides a real opportunity for Belgian teams to have an impact on the international scene in this highly competitive sector. ‘We can’t launch these types of projects without collaborators from all over Belgium," Prof. Maltoni emphasises.