Fig. 1.

Activation of cell death pathways in IAV-infected epithelial cells. Following IAV infection, the viral protein NS1 inhibits apoptosis by activating the PI3K/Akt pro-survival pathway, therefore leading to increased viral replication. Later, viral proteins, predominantly NP, activate caspase signaling to facilitate viral protein packaging and virion production, leading to viral egress and consequentially apoptosis. Unknown viral factors induce necrosis through unelucidated mechanisms, causing enhanced inflammation. Finally, IAV-infected epithelial cells undergo necroptosis, a programmed form of necrosis involving the proteins RIPK3 and MLKL. By eliminating the natural replicative niche of the virus, necroptosis helps limit viral replication. Solid arrows indicate both direct viral and host effects, while dashed arrows indicate indirect by-products.