Molecular mechanisms whereby a pandemic influenza A virus antagonizes host antiviral immune responses Grant uri icon


  • The 1918 influenza A virus (1918 IAV) caused the worst pandemic in human history, also known as the "Spanish flu", resulting in more than 50 million deaths. The nonstructural protein 1 (NS1) is a multifunctional virulence factor of IAVs and has been identified as one of the molecular determinants of high pathogenicity of the 1918 IAV(1-3). One important pathway by which the 1918 NS1 enhances its virulence is through hyperactivation of the host phosphoinositide 3 kinase (PI3K) resulting in inhibition of cellular apoptosis(4-10). Unlike NS1 of common seasonal IAVs, the 1918 NS1 dramatically enhances its binding affinity for PI3K by forming a heterotrimeric complex with another host signaling protein CRK (1918 NS1-CRK-PI3K complex) (Fig. 1). The interaction of NS1 with host CRK is also highly conserved in avian and swine IAVs. Therefore, the NS1-PI3K interaction is crucial for understanding the strain-specific host infectivity of IAVs. Highly pathogenic influenza outbreak is a serious threat not only to humans but also to poultry and poultry industry(11). However, the molecular basis of regulation of NS1 interaction with PI3K and CRK is unknown

date/time interval

  • 2019 - 2024