As an airborne virus, influenza A is a widespread threat to global economies and a consistent danger to public health. Through high reassortment and evolutionary rates, influenza is even able to infect those who have been previously vaccinated against the virus. The innate immune system serves as a key first line of defense against this pathogen, with the signaling components, called interferons, driving the production of a potent cellular antiviral response. Studies have indicated that viral populations replete in defective virus particles, virions with a deletion in a portion of their genome, are less efficient at blocking the antiviral response, as shown by increased interferon in the host. Our project seeks to explore this phenomenon of RNA deletions leading to increased interferon expression in host cells by testing the hypothesis that deletions in the three polymerase genes of influenza alone are sufficient to cause an increase in the interferon response. In addition, we are currently testing if mutational deactivation of one of the other genome segments, or absence of such segments, is capable of producing a more robust immune response when combined with polymerase gene deletions. In order to support this analysis, I began by creating pure populations of PA defective influenza particles grown on PA expressing host cells. Similar to results observed by my mentor Dr. Alistair Russell with PB1 and PB2 defective populations, it was found that these PA defective influenza particles were sufficient to induce the interferon response. Recently, I have assisted in the creation of multiple influenza protein expressing cell lines and influenza populations with simultaneous modifications to the HA, NS, and polymerase genes. It is hoped that immune stimulation data derived from these custom viruses, in combination with previous findings, will improve current antiviral therapies and models of the human immune response to influenza.