Immunosuppressive capabilities of Influenza A Virus might be related to the origin of the viral NS1 protein

Background: The viral non-structural protein 1 (NS1) plays a key role in modulating the innate immune response during influenza A virus (IAV) infection enabling the virus to suppress early host defences to establish infection. NS1 is a multifunctional protein that primarily antagonizes type I and type III interferon (IFN) responses by interfering with viral RNA recognition and by disrupting the function of key IFN-stimulated genes (ISG). The immunosuppressive capabilities of NS1 affect how individuals respond to and recover from an infection, but the fundamental mechanisms of how immune evasion by NS1 differ between IAV strains remain to be fully understood.
Methods: Human and porcine airway epithelial cells grown in 24-well plates were infected with four IAVs with a MOI of 0.01 and incubated for 1 hour at 37 °C and 5% CO2. The viruses were of swine origin differing in their NS gene segments (pandemic (pdm09) origin or Eurasian avian-like swine origin, see Table 1). After incubation, virus inoculum was removed and fresh infection media was added. Cells and media were collected at 24, 48, and 72 hours post infection. Antiviral gene expression was analyzed by microfluidic qPCR (Biomark, Fludigm) and viral titers were determined by plaque assay.
Results: Assuming that better immune evasion is correlated with higher viral titers, the pandemic NS1 has an advantage over the Eurasian avian-like swine NS1. Viral pattern recognition receptors (PRRs), cytokines, and ISGs were induced in both human and porcine cells after all infections, but cells infected with IAV with NS gene segments of pandemic origin demonstrated high expression levels of several antiviral immune genes. In contrast, IAV with NS gene segments of Eurasian avian-like swine origin barely expressed any antiviral factors despite infectious virus were demonstrated after all infections.
Conclusions: The immunosuppressive capabilities of IAV might be related to the origin of the viral NS1 protein, as the innate antiviral transcriptional response profiles remained largely conserved when the origin of the NS gene segment was the same.