Exploited defense–How influenza virus hijacks cellular signalling responses

Cell fate decisions in response to extracellular agents, including pathogenic invaders are commonly mediated by intracellular signaling cascades that transduce signals into stimulus specific actions, e.g. changes in gene expression patterns, alterations in the metabolic state of the cell or induction of programmed cell death (apoptosis). Many of these signaling pathways are also activated in response to influenza virus infections. With regard to the function of these responses the overall picture that has emerged suggests that most of the signaling events are initiated as a cellular response to defend the invading pathogen. While at one hand influenza viruses have evolved strategies to keep these antiviral responses in a tolerable limit there is accumulating evidence that the virus also has acquired the capability to exploit some of the remaining activities to ensure efficient replication. To illustrate this concept, some examples will be discussed with regard to influenza virus induced NF-kappaB and PI3K signaling and how the pathogens take advantage of these activities within the infected cell to support propagation. Furthermore, first approaches to exploit these viral dependencies on cellular factors towards development of novel antiviral strategies will also be presented.