Examining the role of the host helicase DDX56 during Flavivirus infections

• Author / Creator

  Reid, Colleen R.

• Flaviviruses, such as West Nile virus (WNV), Powassan virus (POW), and Saint Louis encephalitis virus (SLEV), are significant pathogens capable of causing serious neurological disease in both humans and animals. Despite their relevance to human health, treatment and vaccines for these viruses remain limited. Characterizing important cellular host factors during viral infection may identify novel targets for the development of antivirals. Previously, a host nucleolar RNA helicase, DDX56, was identified as an essential host factor for WNV infectivity by utilizing its ATP-dependent helical activity to enhance the packaging of viral RNA. Through extensive microscopy analyses I show that DDX56 localizes to the ER, the site of viral replication and assembly, during WNV infection and colocalizes with markers for viral assembly. Additionally, DDX56 does not play a role in the reorganization of membranes and the induction of viral structural elements in WNV infection. Together, these data support the role of DDX56 in assembly of infectious virions. I also investigated whether other viruses, POW and SLEV, utilize DDX56 during infection making it a potential target for broad-spectrum antivirals. Interestingly, while I discovered that these viruses affect DDX56 localization and stability, they do not require this helicase for the production of infectious virions. Thus, DDX56 seems to be an essential host factor for WNV while the underlying mechanism of relocalization may not be virus specific. Collectively, my studies further our understanding of the role of DDX56 during WNV infection and further support it as a target for the development of antivirals.

• Subjects / Keywords

  • Viral-host interactions
  • Flavivirus
  • RNA Helicases

• Graduation date

  Spring 2016

• Type of Item

  Thesis

• Degree

  Master of Science

• DOI

  https://doi.org/10.7939/R3639KH98

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.