Details

Autor(en) / Beteiligte

• Munoz-Basagoiti, Jordana

Titel

Investigation of the Roles of Ebola Virus RNA- Dependent RNA Polymerase and Its Co-Factor VP35 With the Host

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2019

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Ebola virus (EBOV) was first identified in 1976 and, since then, small outbreaks have been occurring in central and West African countries. The largest EBOV outbreak until now, taking place from year 2013 to 2016, left more than 28.000 cases and 11.000 deaths. EBOV is a highly contagious and virulent pathogen with no FDA-licensed therapeutic available yet. Huge efforts are currently being made for the development of effective antiviral therapeutics and the investigation of viral evolution dynamics in correlation with its virulence. Viruses are obliged parasites of the host cell in order to accomplish every stage of their biological life cycle. For viral RNA synthesis, occurring in the cell cytoplasm, Ebola virus must interact with host proteins, which at the same time can be exploited as potential antiviral targets. In this study, coimmunoprecipitation and high-throughput label-free proteomics are used to elucidate novel protein associations between EBOV VP35, L and host factors. Biological importance of the host proteins DYNLL1 and CALM on Ebola virus life cycle is assessed by using small molecule inhibitors in an EBOV minigenome system in cellular culture, resulting in a significant decrease of viral replication when either of the cellular factors is antagonised. The study of VP35 is taken further and the phenotypic changes on the protein functionality during the early beginning of the 2013-2016 West African outbreak are characterised, demonstrating slight differences on the viral protein performance that could help understand better Ebola virus virulence. Overall, this thesis provides a better understanding of the interactions that Ebola virus establishes with its host, the implications that single mutations can have on viral proteins functionality and the EBOV pathogenesis.