Influenza virus affects apoptosis: Identifying targets for therapy

Influenza virus infection is an infectious disease, especially dangerous for immunocompromised patients and the elderly. This disease is the cause of many fatalities each year during the annual flu outbreaks and can potentially result in the deaths of millions if a dangerous pandemic strain appears in the population. The body’s immune system fights the influenza infection via several mechanisms, one being the induction of apoptosis, the regulated form of cell death. However, the influenza infection also seems capable of influencing the apoptosis pathways, probably to improve the virus propagation. Identification of the effect influenza infection has on the apoptosis pathways could lead to new ways to fight or prevent the infection. Influenza infection affects an anti-apoptotic pathway, the viral protein NS1 causes an activation of the P13K/Akt pathway. This occurs mostly in the earlier stages of the infection. Influenza infection also has effects on the pro-apoptotic pathways by inducing p53, TRAIL, FasL, caspase-3 and cytochrome c release from the mitochondria, which are all factors that lead to an increase in apoptosis in the cell, during the later stages of infection. Most of these effects appear to be a reaction of the host’s body to the influenza infection, only the release of cytochrome c seems to be a direct response to a viral protein, PB1-F2. The upregulations caused by the host do seem to be profitable for the virus, since downregulation of TRAIL, FasL and caspase-3 all cause the viral propagation to decrease. Thus, influenza appears to activate anti-apoptotic pathways to prevent early clearance of infected cells and induce apoptosis through pro-apoptotic pathways later in the infection to provide necessary factors for efficient virus propagation. Targeting the factors influenza affects could lead to new ways to fight influenza infection, although much research is necessary before this is a realistic approach.