Viral inflammation: Sensing, signaling, safeguarding: DENV and SARS-CoV-2

Bram ter Ellen

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    This thesis is dedicated to the study of the interactions of these viruses with human cells. It focuses on investigating DENV infection in host immune cells, along with the immune responses it initiates and how they develop. Furthermore, the work centers on the study of SARS-CoV-2 infection in various cell models, while also examining whether the infection can be inhibited with potential antiviral agents.

    This thesis revealed the critical role of Toll-like receptor 2 (TLR2) in severe DENV infections, particularly its association with classical monocytes and disease progression. Furthermore, it delved into antibody-dependent enhancement (ADE) in DENV infections, emphasizing TLR2's pivotal role in mediating viral entry and triggering inflammatory responses, along with the contributions of TLR8, TLR3, and SYK.
    Furthermore, this thesis presents compelling evidence of the antiviral properties of resveratrol and pterostilbene against SARS-CoV-2, offering promising therapeutic avenues. However, it issues a word of caution regarding the use of ivermectin and moxidectin for against SARS-CoV-2, underlining the limitations of in vitro results and their applicability to human respiratory epithelial cells.
    In addition, we have demonstrated that human lung microvascular endothelial cells are not susceptible and permissive to SARS-CoV-2 infection, and that virus exposure to endothelial cells does not lead to endothelial activation.

    Collectively, these chapters offer a comprehensive exploration of the complex interactions between viruses and the human immune system, yielding novel insights into potential therapeutic strategies and enhancing our broader understanding of viral diseases. These findings underscore the significance of both in vitro and in vivo research, providing valuable implications for the development of antiviral therapies and the management of viral diseases."
    Originele taal-2English
    KwalificatieDoctor of Philosophy
    Toekennende instantie
    • Rijksuniversiteit Groningen
    Begeleider(s)/adviseur
    • Smit, Jolanda, Supervisor
    • Rodenhuis-Zybert, Izabela, Co-supervisor
    • Moser, Jill, Co-supervisor
    Datum van toekenning15-dec.-2023
    Plaats van publicatie[Groningen]
    Uitgever
    DOI's
    StatusPublished - 2023

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