UCLouvain researchers have discovered the essential role played by a glycoprotein present on the surface of herpesviruses. These viruses are responsible for several diseases, which are potentially serious for some individuals, yet treatments are lacking.
The herpesvirus family includes viruses responsible for cold sores (oral herpes), chickenpox, shingles and even mononucleosis. As unpleasant as they are, they’re usually benign for healthy individuals – so much the better, because while we have an array of antibiotics to fight Pathogenic bacteria, we have few antiviral drugs.1 In cases of viral illness, aside from resting and ‘waiting for it to pass’, not much can be done. Which poses a problem: the same diseases can be dangerous when they strike immunocompromised individuals (HIV-positive persons, cancer patients, etc.) or fetuses.2 Hence the interest in better understanding them in order to develop antiviral drugs.
When the virus ‘tests the waters’
A viral infection occurs when a virus manages to break into a cell in order to duplicate it. This process takes place in several stages. ‘The first step is for the virion to dock with the cell in question and check whether they’re compatible’, says David Alsteens, an FNRS researcher and professor at UCLouvain’s Louvain Institute of Biomolecular Science and Technology (LIBST). ‘To do this, some glycoproteins on the surface of the virion interact with receptors in the cell membrane. It’s a bit like the beach game where you throw a fluffy ball (the virus) at a Velcro racquet (cell). The Velcro represents the links between viral glycoproteins and cellular receptors. In our jargon, we call this type of interaction multivalence. It’s a key concept for understanding the first stage of viral infection.’
Not too much Velcro!
The glycoproteins (gps) of viruses differ according to virus type and are poorly known. Herpesviruses, for example, have about 15 different gps; the roles of only one-third of them have been clearly identified. Martin Delguste is an FNRS candidate and carries out his research in the laboratory of Prof. Alsteens. In collaboration with Prof. Laurent Gillet of the University of Liège, he focused on the largest gp, gp150. ‘We discovered that it plays a modulator role’, Prof. Alsteens says. ‘It manages the number of links, of interactions, between other herpesvirus gps and cell receptors.’
This is a crucial function for the virus. Indeed, it must be sufficiently ‘velcroed’, or attached, to the cell – but not too much. If there are too many links, the virion is hindered. It must be able to move on the surface of the cell to find the access routes that will allow it to get inside. ‘A bit like the virus tries its keys in the locks of the cell’s different doors. If it can’t properly move on the cell surface, it can’t try all the available doors.’ Thus gp150 serves to find the right balance in multivalence, by managing the quantity and strength of virus-cell links.
A target for new antivirals?
Until now, researchers didn’t know that the virus can regulate the number of links with the cell it aims to infect. Understanding gp150’s modulator role is a real discovery. It was the subject of a recent publication in the prestigious journal Science Advances.3 ‘We now have to discover the roles of other gps’, Prof. Alsteens said. ‘That being said, gp150 could be a good target for an antiviral drug.’ Indeed, a molecule could possibly sabotage gp150 and prevent the virus from establishing the right number of cell receptor links, which would prevent the virus from docking with the cell or moving freely, thus preventing infection. It’s a hypothesis in need of testing.
(1)Except vaccines intended to prevent certain viral diseases. (2)Cytomegalovirus (a genus of herpesviruses) is particularly feared by pregnant women. (3)M. Delguste et al., ‘Multivalent binding of herpesvirus to living cells is tightly regulated during infection’, Science Advances, 16 August 2018.
A glance at David Alsteens's bio
2007: Master’s Degree in Chemical Engineering and Bioindustry, UCLouvain
2011: PhD in Bioengineering, UCLouvain; thesis award winner, Royal Belgian Society for Microscopy
2011-13: FNRS Researcher, UCLouvain
2011-15: Associate Professor, UCLouvain
2013-15: Researcher, ETH Zurich (Swiss Federal Institute of Technology)
Since 2015: FNRS Research Associate
Prof. Alsteens’s research has been financed mainly by FNRS and Europe through an ERC Starting Grant.