Differences in Flavivirus NS1 Phenotype
Open Access
- Author:
- Toner, Shay
- Area of Honors:
- Microbiology
- Degree:
- Bachelor of Science
- Document Type:
- Thesis
- Thesis Supervisors:
- Joyce Jose, Thesis Supervisor
Lorraine C Santy, Thesis Honors Advisor - Keywords:
- dengue virus
Zika virus
flavivirus
NS1
Flaviviridae
deer tick virus
actin remodeling - Abstract:
- The family of viruses known as Flaviviridae includes several well-known human pathogens that are primarily spread through arthropod vectors, and includes the dengue, West-Nile, deer tick, and Zika viruses among others. These viruses have been responsible for disease outbreaks around the globe, and with warmer temperatures resulting in a wider distribution of vectors, understanding the pathogenesis of these viruses is more important than ever. Flavivirus genomes are small, encoding a variety of structural (C, prM and E) and nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) that are essential to the replication and survival of the virus. Among these proteins is NS1, which plays a role in both replication and immune evasion. This protein is extremely highly conserved amongst flaviviruses, with few differences in amino acid composition between different species. This work examines differences in cell phenotype upon expression of NS1 from different flaviviruses, including a previously unknown behavior of the Zika NS1 protein. Copies of four different viral NS1 were expressed from a mammalian expression plasmid pcDNA 3.1 + form with an affixed fluorescent tag to allow for cell imaging upon transfection. Chimeric NS1 proteins were also produced in order to determine the regions responsible for differing NS1 behaviors. Results indicate that specific regions in the N-terminal region of Zika NS1 differentiate it from the NS1 of other flaviviruses and allow it to induce actin remodeling upon expression in a host cell.