Characterization Of Influenza Virus Nonstructural Protein (Ns1) Effect On Viral RNA Expression

RM 217

Influenza is a negative single strand RNA virus of economic and global health concern because it quickly evolves to evade vaccines and adapt resistance to antiviral therapies. While yearly vaccination is required to control seasonal influenza, pandemic prevention relies on effective antivirals. Resistance has been documented for the current approved antivirals which prevent influenza. To reduce the chance of resistance, our laboratory aims to target multiple interaction domains within the influenza nucleoprotein (NP), a highly conserved protein among influenza subtypes. This project aims to establish if the viral nonstructural NS1 protein enhances viral RNA expression through interaction with the N-terminus of NP. This will be done by transfecting 293T cells with DNA plasmids to express viral ribonucleoprotein complexes, responsible for viral RNA expression, with either WT-NP or NP with deletion of the N-terminal 20 amino acids in the presence or absence of NS1 for comparison. RNA will then be isolated from the transfected cells to determine whether NS1 influences viral RNA production and if this effect requires the N-terminus of NP. Our data will determine if NS1-NP interaction is important for viral RNA expression and a potential antiviral target to facilitate development of novel antiviral therapies. If we prove this true, the next step will be to prevent the NS1-NP protein interaction and confirm inhibition of viral infection.