Insufficiency in airway interferon activation defines clinical severity to infant RSV infection

Chin-Yi Chu; Xing Qiu; Matthew N. McCall; Lu Wang; Anthony Corbett; Jeanne Holden-Wiltse; Christopher Slaunwhite; Qian Wang; Christopher Anderson; Alex Grier; Steven R. Gill; Gloria S. Pryhuber; Ann R. Falsey; David J. Topham; Mary T. Caserta; Edward E. Walsh; Thomas J Mariani

In vitro, our data indicating that IFN is both necessary and sufficient to control RSV infection of mammalian cells is not particularly novel, but validates the hypothesis generated by our in vivo data. However, we feel that it is important to demonstrate this mechanism is causal for infection in a truly physiological model of bona fide human pediatric lung epithelial cells. These in vitro data also partially reveal the complexity of the in vivo response, in that only a subset of gene expression correlates of severity are validated. We suggest other severity-associated gene expression responses require, or result from, additional cell types (e.g., leukocytes), and likely to be modified by the microbial community. Modeling these states and responses are one focus of future experimentation.