Virology

We try to translate basic knowledge into new methods to prevent or treat virus infections

The class of RNA viruses includes many (emerging) pathogens of humans and animals. As such, they are a major cause of morbidity and mortality and responsible for huge economic losses worldwide.

Coronaviruses, Influenza A viruses, and Picornaviruses
In the Virology research group, we study the following RNA viruses:

  • Coronaviruses - including zoonotic threats like SARS-CoV and MERS-CoV, but also important animal pathogens like PEDV and FIPV
  • Influenza A viruses - for instance avian influenza A viruses which can cause bird flu, but also pose threats to humans by zoonotic infections
  • Picornaviruses - for instance enteroviruses, rhinoviruses, EMCV, and FMDV

We perform research at the level of molecules, cells, tissues, and organisms, to unravel the structure of these viruses and to identify their cellular receptors, entry pathways, replication mechanisms, assembly and release pathways, immune evasion strategies, as well as the mechanism of disease caused by these viruses (i.e. pathogenesis).

Furthermore, based on our intensive studies in glycans (e.g. sialic acids) as virus receptor, we have established strong scientific and technological expertise in the field of “glycovirology”.

Our ultimate goal is to translate the knowledge that we obtain into the development of novel vaccines, antiviral therapies, and diagnostic tools.

Virus Structure, Receptors and Entry Mechanisms

Coronavirussen

We focus on virus structures, virus-cell attachment, endocytic uptake of virus particles, fusion between viral and host membranes, and the mechanism of genome release. To this end, we developed novel systems for the expression of recombinant viral attachment/ fusion proteins, which are applied to study the interaction of viruses with their receptors. Our multidisciplinary approach entails molecular virology (reverse and forward genetics), structural biology (crystallography, EM), glycobiology (e.g. glycan array analysis), biophysics, biochemistry, cell biology (e.g siRNA screens and haploid cell screens), bio-informatics, and in vivo studies.

Glycovirology

Among host cell surface determinants for pathogen attachment, sialic acids rank prominently. With picorna-, corona- and influenzaviruses as models, we aim to understand how viruses cope with the many complexities related to adherence to sialoglycans, e.g. how viruses escape irreversible binding to decoy receptors, how they distinguish decoys from bona fide entry receptors, and how viral adaptation to particular sialoglycans affect pathogenicity, spread, and cross species transmission. We have unique expertise in the analysis of protein-sialoglycan interactions and offer a range of assays (glycan array analysis, lectin binding assays, Bio-Layer Interferometry) with natural and designer glycoconjugates, as well as a toolbox of recombinant virus attachment proteins (‘virolectins) en enzymes for explorative sialoglycobiology.

Virus Replication

Making use of state-of-the-art virological, biochemical, cell biological (e.g. siRNA and haploid screens), and microscopy (e.g. life cell imaging and EM tomography) approaches, we study the role of picornavirus proteins and (hijacked) host factors in the formation and the architecture of the viral replication organelles as well as in the process of viral RNA synthesis that takes place in these specialised replication sites.

Vaccines and Antiviral Drugs

We develop innovative vaccines for coronaviruses and influenza A viruses using recombinant protein and virus-like particle technology as well as live attenuated virus approaches. As there are very few effective antiviral drugs to treat enterovirus and rhinovirus infections (for which it is impossible to develop vaccines given the large number of serotypes), we also aim to identify potent, broad-range and safe inhibitors of enterovirus/rhinovirus replication and to elucidate their mode of action.

Innate Antiviral Responses

We study how intracellular RNA sensors (e.g. RIG-I, MDA5, PKR) discriminate viral RNA from host cell RNA and how they signal to activate IFN-α/β responses and stress responses to combat virus infection. Conversely, we investigate how picornaviruses and coronaviruses actively manipulate these intracellular signaling pathways to suppress these infection-limiting innate host responses.

Clinical Virology

We study aspects of virology that are related to virus-induced disease in the host including diagnosis, pathogenesis, epidemiology, treatment and prevention. We focus on virus infections of companion animals more specifically coronavirus and retrovirus infections, making use of the expertise and tools generated in the other focus areas of our research. Besides studies on naturally-infected animals we have developed challenge models in the cat for FIP, FIV and FeLV to investigate the different aspects of virus-host interaction.

Group members