MAVS is Important for Antiviral Defense Against InfluenzaA Virus in a Human Respiratory Epithelium Model

The respiratory epithelium is an important immunological barrier and the first line of defense against influenza A virus. In mice and in various cellular systems, induction of type I interferons (IFN/{beta}) during IAV infections is known to depend on cytosolic RNA sensors RIG-I and MDA5 and on the adaptor molecule MAVS. Until now, it has not been possible to directly test the importance of MAVS for induction of IFNs and for resistance to IAV infection in primary human respiratory epithelium. Here, we used CRISPR-Cas9 to establish MAVS-deficient cultures of primary human respiratory epithelium using the air-liquid interphase culture system. Using this setup, we show that MAVS is indeed required for the induction of type I and type III IFNs and subsequently for the induction of IFN-stimulated genes in response to IAV infection in human primary respiratory epithelium. Finally, we demonstrate that MAVS is important for restricting viral replication in this model. In conclusion, we demonstrate that MAVS plays a non-redundant protective role during IAV infection in primary human respiratory epithelium.