Browsing by Author "Pulkkinen, Lauri"

Host factors play crucial roles in virus infections. Viruses exploit various cellular processes and are counteracted by an arsenal of host antiviral defenses. Characterization of these interactions is crucial for understanding the viral life cycle and developing novel antiviral treatments. Semliki Forest virus (SFV) is a positive-strand RNA alphavirus that has been used as a model virus for multiple clinically significant diseases such as lethal encephalitis. The aim of this thesis was to identify host factors that affect SFV infection to better understand the biology of SFV, and to provide candidate targets for therapies against more serious alphavirus infections. Here I have conducted follow up studies on a previously performed genome-wide siRNA screen that hinted that a number of genes have novel functions in SFV infection. I used an automated high-throughput imaging-based approach to confirm the roles of these host factors in SFV infection. For comparison, I also used a similar strategy to test if these genes affect negative-strand RNA virus infections, using vesicular stomatitis virus (VSV). Additionally, I studied whether the host factors affecting SFV infections perform their roles in the entry and penetration, or post-penetration steps using a previously developed endocytic bypass assay. I identified the γ-aminobutyric acid (GABA) transporter, SLC6A13, as a potential receptor for SFV. I also describe other novel genes that have roles in SFV or VSV infections. In addition, I show that TNP01, RPL18, ETF1, DMN2, and GNDPA1 promote, and HDAC6 counteracts SFV infection in the entry and membrane penetration steps. Furthermore, I report that in the later stages of the infection DDX54 boosts and EIF2B3, EIF4G1, PHB2, EDF1, DDX47, and DHX57 hinder SFV.