Alsteens, DavidNysten, BernardLe Brun, GrégoireGrégoireLe Brun2025-05-142025-05-142025-05-142018https://hdl.handle.net/2078.2/4249Viruses are a major class of pathogens and have been identified to infect a variety of organisms. As they cannot reproduce themselves, their replication critically depends on the ability to enter a host cell and insert their genomes to a replication site. The cell imposes multiple barriers to virus entry, including the plasma membrane. As a result, viruses have developed various strategies to overcome these barriers and gain entry to cells to replicate and propagate infection. Virus entry is largely defined by the preliminary interactions between virus particles and their receptors at the cell surface. Detailed information about these molecular mechanisms between viruses and host organisms is required to develop strategies to block virus attachment before they enter the cell. Herpesviruses are ubiquitous and associated with several well-known diseases. In comparison with other viruses, herpesviruses present complex molecular mechanisms of entry. Efficient infection of host cells requires multiple viral glycoproteins and involve multiple host cell receptors. For its first attachments on host cells, murid herpesvirus 4 (MuHV- 4), closely related to the human gammaherpesviruses, is known to bind cell surface glycosaminoglycans through two viral glycoproteins, gH/gL and gp70, but their detailed contribution is not fully understood yet. Atomic force microscopy (AFM), initially developed for imaging inert materials at the nanoscale, has evolved in a powerful tool in nanobiotechnologies. Single-virus-force-spectroscopy (SVFS) AFM mode now allows to probe and measure the interactions between a single virus and its cellular receptors directly on living cells. Combining SVFS with biophysical models describing the physics of bond dissociation, we studied MuHV-4—cell surface receptor interactions and obtained quantitative measures of the kinetics of the bonds involved between gH/gL and their cellular receptors. Our results showed that gH/gL is the major MuHV-4 glycoprotein involved in the attachment to cells, therefore playing a crucial role in virus infection.HerpesvirusVirus entryNanotechnologiesAtomic force microscopyBiophysicstext::thesis::master thesisthesis:14897