Avian and Human Influenza A Virus Non-Structural Protein 1 in Innate Immune Response Inhibition

Abstract

Influenza viruses are respiratory pathogens responsible for seasonal epidemics. In addition, influenza A viruses (IAVs), which infect a wide range of animals, can cause emerging zoonotic pandemics. Recently, the avian H5N1 IAV subtype has widely spread in birds and mammals, raising concerns about adaption to humans and pandemic potential. An important part of the host's antiviral response against IAVs is the retinoic acid-inducible gene I (RIG-I) receptor, which triggers the production of IFNs to limit viral replication. To overcome the host's antiviral response IAVs encode non-structural protein 1 (NS1). The aim of this thesis project was to compare how the NS1 proteins of thirteen different IAV strains, including both human- and avian-infecting strains, inhibit the RIG-I induced IFN-λ1 promoter activation. NS1 proteins were expressed together with constitutively active ΔRIG-I that activates the RIG-I pathway, and their expression was confirmed with western blot and immunofluorescence assay. Inhibition of the IFN-λ1 promoter activation by expressed NS1 proteins was quantified using a luciferase assay. All thirteen NS1s showed inhibition of the IFN-λ1 promoter activation, although their expression levels varied. Differences between NS1 proteins from different IAV strains were also observed. This project has provided more insight into the differences in NS1 protein function between various IAV strains, laying the groundwork for further research. A better understanding of NS1 function could clarify how IAV strains adapt to new host species and facilitate the development of countermeasures against IAVs.