Against pathogenic bacteria, we have antibiotics. Against viruses, we have vaccines and some antiviral drugs. And against cancer, we may soon have ... viruses! ‘A viral infection means that a virus has managed to get into a human cell and duplicate it’, says Prof. Alsteens, an FNRS research associate who heads UCLouvain’s NanoBiophysics Lab. ‘We know that some viruses are oncolytic. That is, they can infect cancer cells and, if so, destroy them. That's the paradox of – and interest in – research on viruses: we seek to know them better in order to neutralise them or, on the contrary, use them as therapeutic tools.’
AFM: closest to the real
To do this, Prof. Alsteens and his team have worked for several years with atomic force microscopy (AFM). ‘This technology works a bit like a record player’, he says. ‘Its very fine point sweeps the sample and measures its relief, with a precision close to one nanometre (one billionth of a meter). On such a small scale, it’s possible to study unitary structures: a cell and one or two virions.’
The team has also developed and patented an analysis chamber. This small box can be regulated very precisely in terms of temperature, pH, humidity, oxygen concentration, CO2, etc. Using it in tandem with AFM, Prof. Alsteens's team was able to begin studying interactions between viruses and living cells. ‘This is the advantage of AFM over previous technologies. With an electron microscope, for example, the samples must be fixed before being analysed. There’s no movement. But by combining an AFM tip with an optical microscope, we can observe live samples. And thus be closer to real natural conditions.’
At the NanoBiophysics Lab, half the researchers – about ten people – study interactions between viruses and cells. ‘We’re particularly interested in the earliest phases of these interactions, in the very first contacts between a virion and a cell surface’, Prof. Alsteens explains. ‘Since 2015, AFM has enabled us to obtain exciting results!’ Results that have earned him the Heinrich Emanuel Merck Award for Analytical Science in September and the BAEF Alumni Award, on 28 November. His team’s discoveries are also regularly published, the latest in the prestigious journal Nature Communications.
For this research, Prof. Alsteens's team looked at reoviruses. These viruses are good models for studying rotavirus, which is responsible for certain forms of gastroenteritis, and which are part of the same family. ReovirusReoviruses are also involved in celiac disease (gluten intolerance) and have oncolytic potential.
Key, lock and sugar
‘In order to enter the cell, the virion must insert its key (sigma-1) into the cell lock (the JAM-A receiver)’, Prof. Alsteens explains. ‘Now, normally, this key is folded. We wanted to know what unfolded the key when the virion comes into contact with the cell.’
Thanks to AFM technology, researchers found the answer. ‘There’s a whole series of sugars on the cell membrane. We hadn’t paid much attention to them because we didn’t think they played an important role in virus-cell interaction. We were wrong! Indeed, we discovered that the virion binds first with one of these sugars, sialic acid. And it’s this linkage that unfolds the key.’
Identifying and learning more about the mechanism will create very interesting possibilities. ‘Understanding the early stages of viral infection may ultimately allow us to modulate it’, Prof. Alsteens says. ‘For example, if we use reovirus as a weapon against cancer cells, we would be well advised to find a way to "boost" the likelihood of viral infection. Such research is also under way.’