Research Day
EBOLAVIRUS PATHOGENESIS: COULD PROTEASE-ACTIVATED RECEPTORS BE THE POTENTIAL LINK BETWEEN THE IMMUNE RESPONSE AND COAGULOPATHY?
Document Type
Abstract
Date
2021
Abstract
Background: Ebola is a devastating viral disease that has claimed lives and destroyed communities far past the well-publicized 2014 outbreak. Despite the continued prevalence of this virus and advances in vaccines, the pathogenesis of Ebola still isn't completely understood, in part due to limitations imposed by its biosafety-level 4 status. Currently it is unclear how coagulopathy and the inflammatory response correlate. Protease-activated receptors (PARs), while not directly immune receptors, potentially regulate the immune response through a shared signal transduction cascade. Ebola viral infection causes an increase in coagulation cascade proteases which are known activators of PARs. PARs are currently unexplored in the context of Ebola pathogenesis.
Methods: This study provides an untested theoretical model based on the literature for how PARs may connect the coagulopathy and inflammatory responses seen during Ebola infection.
Results: Activation of PAR2 leads to increased cytokine production, decreased anti-viral response, and altered vascular function; which mirrors the response seen during Ebola infection. The PAR2 mediated effects work in combination with Toll-like Receptor 4 (TLR-4) which is activated by Ebola viral glycoprotein. The presence of PAR2 and TLR-4 on macrophages could together explain a link between coagulation abnormalities and immune response during an Ebola infection.
Conclusion: The pathogenesis of Ebola is very complex and challenging to study, thus development of literature-based models can provide direction for future studies. Understanding the connection between coagulation and the immune response to infection with Ebola can help guide treatment and will lead to a better understanding of Ebola pathogenesis.