INFLUENZA A VIRUS STIMULATES AUTOPHAGY TO UNDERMINE HOST CELL IFN- PRODUCTION

Autophagy is originally described as the main catabolic pathway responsible for maintaining intracellular nutritional homeostasis that involves the formation of a unique vacuole, the autophagosome, and the interaction with the lysosome. Recent evidence indicated the essential role of the host autophagy, in enhancing influenza A virus (IAV) replication in human lung epithelial cells. Here, findings demonstrate that IAV infection increased levels of the autophagosomal marker ``microtubule-associated protein light chain 3-II`` (LC3-II), at early stage of infection. Further, knockout of Atg5, the crucial components of autophagosome formation, and siRNA- mediated depletion of autophagy related genes Atg9, Atg12, Atg16, provide further evidence on the essential and supportive role of autophagy in IAV replication. Interestingly, in autophagy-deficient cells (Atg5-/- MEFs), and A549 cells lacking autophagy levels of host protective type I interferons, in particular IFN-�, were increased during infection. Taken together, these data further confirm the beneficial role of autophagy for IAV infection may be via regulation of IFN-� production and highlights autophagosome formation as a potential novel antiviral target.