Fig 1.
How zoonotic IAVs can overcome anti-IAV restriction factors.
Avian IAVs are poorly adapted to the human host. This species barrier prevents individual infections (1). Deficiencies of anti-IAV restriction factors or defects in their activation like loss of IFN induction or signaling required for the expression of antiviral ISGs can increase the susceptibility of individual humans to zoonotic IAVs (2). Zoonotic IAVs can also exploit different adaptation strategies to evade antiviral restriction factors including the acquisition of escape mutations (3) or replication enhancing mutations resulting in highly potent NS1 variants antagonizing the IFN response (4) or increased viral polymerase activity (5). Created with BioRender.com. IAV, influenza A virus; IFN, interferon; ISG, IFN-stimulated gene.