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

The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/641795 doi: bioRxiv preprint An analysis of potential regulators for this gene expression response implicated both type 3 (IFNL1; p<10 −35 ) and type 1 (IFNA2; p<10 −30 ) ligands, as well as the canonical interferon-associated transcription factors IRF-3, -7 and -5 (p<10 −15 ). Due to the low level of expression for many IFN ligand and receptor genes in most subjects, we removed them from our analytical data set, as part of our procedures to avoid false discovery and increase statistical power. We performed a post-hoc analysis of IFN ligand expression and found evidence for high levels of expression for both type 1 and 3 ligands (particularly IFNB1, IFNL1, IFNL2, IFNL3) in non-severe subjects, but not severe subjects (Fig. 3C) . We used multiplex ELISA of nasal washings to measure airway IFN ligand production during the first few days following onset of clinical symptoms. We confirmed higher levels of IFNB and IFNL in non-severe subjects (Fig. 3D) . These data suggest that interferon signaling responses and/or interferon production, within the first few days of infection, contributes to establishing clinical severity in RSV infected infants.