Viruses are small pathogenic particle that rely on hijacking a cellular host to multiply and spread. The viral infectious cycle therefore begins and ends with cell surface interactions, from finding the target cell for infection to the escape of viral progeny.
These interactions are complex dynamic processes requiring a series of fine-tuned biomolecular recognition events. Virus entry, for example, is a multistep processes which may require virus diffusion through the glycocalyx (i.e. the sugar coat covering the cell), virus attachment to the cell membrane and its lateral diffusion to a point of entry; this is followed by cell penetration which involves membrane fusion or the deformation of the plasma membrane into an endocytic vesicle. While such initial recognition is crucial in the viruses’life cycle as it leads to infection, equally important is the capability of the virus to overcome these interactions upon egress, to ensure virus propagation. Such processes are typically mediated my more or less specific biomolecular interactions; they are further modulated by the establishment of multiple bonds between the virus particle and the cell surface (multivalency).
Beyond identifying the individual biomolecules involved in virus-membrane interactions, my research aims at understanding how these biomolecules work together, through multivalency, to fine-tune the different processes leading to viral entry or egress. To do so, my group adopts a multidisciplinary approach combining traditional cell studies used in the field of virology with advanced biophysical approaches. Indeed, we work with minimal models of the cell membrane (cell-membrane mimics), to study processes occurring at the cell surface in a highly controlled manner. Cell-surface mimics are model systems whose composition can be fine-tuned to study specific interactions occurring at the cell surface with great precision and accessibility by many surface-sensitive analytical techniques. As a complement, we perform single particle tracking in live-cell microscopy experiments. Live-cell microscopy allows for interactions to be investigated within the complex milieu of natural components and provide physiological feedback on interactions taking place at the cell surface. Using advanced microscopy, we analyze and quantify the binding kinetics and diffusion behavior of individual viruses. Using force spectroscopy on such systems further allows us to characterize binding strength and number of virus- cell surface contacts formed.
So far, my group has mainly worked with glycosaminoglycan (GAG)-binding viruses (herpes simplex virus in particular), with aim at elucidating the mechanisms by which binding and release from cell-surface carbohydrates is modulated and the processes by which such viruses travel through the GAG-rich glycocalyx without being trapped. Specifically, we are focusing on the regulatory role of viral protein glycosylation to the process and on the role of GAG properites (degree of sulfation etc) in the process.
Understanding the mechanisms by which virus particles recognize, diffuse on, and cross the cell surface is of central importance to the development of new antiviral therapies, new drug delivery vectors and new diagnostic tools.