Deciphering cell-herpesvirus interactions using force-distance curve-based atomic force microscopy
(2021)
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- Authors
- Supervisors
- Alsteens, David
- Abstract
- Viruses are the most numerous species on earth. Some of them can be the cause of mild to severe diseases with potential deadly outcomes. Viral infection is initiated by the attachment of virus particles to the surface of target host cells. Understanding the molecular interactions taking place between virus particles and cell surface molecules is of fundamental interest for the development of new therapeutics interfering with virus attachment processes. Most of the insights gained on virus-cell interactions are currently obtained via ensemble molecular studies providing average responses of populations of virions. To unveil molecular details arising from biological variability, studies performed at the single virus particle-level could provide new valuable insights into virus attachment mechanisms. The aim of this PhD thesis is therefore to implement new tools to decipher the putative roles of viral surface glycoproteins upon attachment to cell surfaces at the single-virus particle level. This work involves the use and development of atomic force microscopy-based single-virus force spectroscopy (SVFS) to decipher the molecular mechanisms of herpesvirus attachment to cell surface glycosaminoglycans (GAGs). We investigated the attachment properties of single virions of Murid Herpesvirus-4 (MuHV-4) and Herpes Simplex Virus-1 (HSV-1) towards both purified GAGs grafted onto inert surfaces and GAGs on living cell surfaces. We observed that both glycoprotein gp150 (MuHV-4) and the mucin-like region of glycoprotein gC (HSV-1) play regulatory roles upon attachment of virions to GAGs, by regulating the multivalency of other viral glycoprotein-GAG interactions. We further deciphered the putative roles of two apparently redundant glycoproteins of MuHV-4: gH/gL and gp70. We showed that gH/gL provides a larger contribution to virus-GAG interactions than gp70 and that the gH/gL-GAG interactions have a higher inherent stability. The molecular insights gained by SVFS on the complex mechanisms developed by herpesviruses to attach target cells could contribute to the development of new antiviral therapeutics potentially targeting specific viral surface glycoproteins.
- Affiliations
Citations
Delguste, M. (2021). Deciphering cell-herpesvirus interactions using force-distance curve-based atomic force microscopy. https://hdl.handle.net/2078.5/107259