Elucidating the Molecular Mechanisms by which Arboviruses Hijack Cellular Pathways

• Author / Creator

  Airo, Adriana M

• Despite their small size and apparent simplicity, viruses are capable of causing mass casualties, political turmoil, and global economic shut down. Due to their minimal genome (~10–12 kb), arboviruses such as Zika (ZIKV), Dengue (DENV), and
  Mayaro (MAYV) depend on many host molecules for replication and have evolved multiple strategies to subvert host innate immune defense mechanisms. Currently, few
  vaccines and limited treatment options exist.

  The main function of flavivirus capsid proteins is to protect the viral genome, however, accumulating evidence suggests that in addition to this function, capsid can modulate the host cell to create a favourable environment for viral replication. A major
  finding in this thesis was that flavivirus capsids play a role in evasion of antiviral systems. Strategies employed by capsid include inhibition of apoptosis and activation of the master regulator Akt. Moreover, I examined the global transcriptome changes in capsid expressing cells by RNA-Seq and identified a potential mechanism by which flavivirus capsids suppress the production of type I interferon.

  Very little is known about the interactions of MAYV with human cells, therefore, in this thesis I examine MAYV tropism and characterize MAYV-infection in primary human macrophages. RNA-Seq data revealed that MAYV causes drastic changes in the transcriptome of infected macrophages and suggests an important role for macrophages in MAYV-induced inflammation and disease pathology.

  Collectively, this thesis provides insight into arbovirus-host interactions. Understanding the consequences of the interactions between viral proteins and cellular factors may reveal novel therapeutic targets.

• Subjects / Keywords

  • Arboviruses
  • Zika virus
  • Capsid
  • Alphaviruses
  • Virus-host interactions
  • Mayaro virus
  • Flaviviruses

• Graduation date

  Fall 2020

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-ec8h-4f28

• License

  Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.