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The copyright holder for this preprint (which was not peer-reviewed) is the author/funder.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 multiple biological functions related to viral infection (Fig. 1A) , confirming the validity of the approach and the data. Interestingly, this analysis suggested that gene expression biomarkers of severity are associated with pneumonia (Fig. 1B) . This observation, consistent with the lower respiratory track pathogenesis of severe RSV infections, also supports the utility of upper airway transcriptome as a surrogate for identifying relevant disease mechanisms in the lung. We also assessed cell signatures in these severity associated gene expression biomarkers. Unlike the epithelial predominant signature of the healthy asymptomatic infant 35 , severe clinical responses to RSV infection were associated with signatures of multiple blood and inflammatory cells, as well as smooth muscle (Fig. 1C) . The most predominant cell signatures were those related to CD14+ and CD33+ myeloid lineages. Pathway analysis confirmed increases in expression of myeloid cell-related genes in severe cases, and also strongly implicated IL17-related responses (Fig. 1D) .