Date of Award

Fall 12-2018

Document Type

Honors Thesis

Degree Name

Bachelor of Science

Department

Biological Science

Advisor/Committee Chair

Cara Pager, Ph.D.

Major

Biology

Committee Member

Gaston Bonenfant

Committee Member

Gabriele Fuchs, Ph.D.

Abstract

In recent years, Zika virus (ZIKV) has taken over mainstream media. It captivated the world with the images of microcephaly babies born to infected mothers and the appearance of Guillain-Barré syndrome emerging from infected adults. ZIKV is transmitted by the Aedes mosquito. This virus is composed of a single-stranded positive-sense RNA genome that belongs to the Flaviviridae family. Our long-term goal is to understand the mechanisms in which the virus subverts the host organism’s translation machinery by modulation of RNA stress granules (SGs). Stress granules are RNA-protein complexes found in the cytoplasm that form when the cell is exposed to a stressor such as an infection from a virus. Our initial research showed that ZIKV suppresses the formation of these granules. Thus the goal of this research was to investigate the role of various stress granule proteins on ZIKV infection. In particular, we focused on TIA-1, G3BP1, HuR and TIAR. Knockdown of the SG proteins with target-specific siRNAs and subsequent infection with ZIKV showed that depletion of G3BP1 decreased viral protein, RNA and viral titers suggesting this SG protein acts in a pro-viral manner, whereas depletion of HuR increased viral protein, RNA and viral titers present suggesting HuR was acting anti-viral. Luciferase assays following knockdown and overexpression of G3BP1 and HuR showed that these proteins affected ZIKV replication. These studies advance our understanding the role and interactions of RNA stress granules with ZIKV.

Download

Included in

Biology Commons

Share

COinS