Biophysical studies of reovirus attachment to host cell receptors using atomic force microscopy
(2024)
Files
Thesis_Rita_dos_Santos_Natividade.pdf
Restricted Access - Adobe PDF
- 9.72 MB
Details
- Authors
- Supervisors
- Alsteens, David
- Abstract
- Viruses pose significant threats to public health and play a critical role in pandemics due to their ability to cause emerging infectious diseases. As obligate intracellular pathogens, viral particles must infect host cells to replicate. A crucial step of the viral life cycle is the attachment to cell surface receptors, which facilitates entry into the host cells and initiates infection. Understanding these interactions is essential for developing strategies to combat viral diseases. In this thesis, we investigate reovirus attachment to host cells, using atomic force microscopy (AFM). The main objective is to elucidate the mechanisms underlying reovirus interaction with cell surface receptors, at the single-molecule level. Single-molecule or single-virus force spectroscopy was used to record the forces and kinetics of reovirus interaction with JAM-A, NgR1, and NRP1 receptors. The first study reveals a stabilizing mechanism in the reovirus T1L – JAM-A complex through addition of GM2 glycans. Furthermore, we found that conformational changes in the σ1 attachment protein can enhance binding to the JAM-A receptor. In the following study, insights were gained into the dynamics of NgR1 binding by reovirus capsid proteins, as well as demonstrated that reovirus stably binds to murine NgR1 at the single-molecule level. Lastly, we provided the first biophysical characterization of the interaction between reovirus and NRP1, showing that reovirus T3D specifically binds to murine NRP1 with high-affinity. Collectively, these studies contribute to a more comprehensive understanding of reovirus infection, which may provide important insights for elucidating the infection process of other virus families and for the development of improved antiviral strategies.
- Affiliations
Citations
Dos Santos Natividade, R. (2024). Biophysical studies of reovirus attachment to host cell receptors using atomic force microscopy. https://hdl.handle.net/2078.5/217480