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

We acknowledge this study is not without limitations. We have focused our efforts in identifying gene expression responses that distinguish infants severely affected by RSV infection as compared to infants who are not severely ill and have not included noninfected controls. Therefore, we are unable to address the specificity of the responses we observe and report. Other studies by our group (Storch and unpublished) suggest that responses to any viral infection can be identified but occur at a much smaller magnitude than those described here. Another limitation is the associative nature of most of the data presented. One must use caution and resist presuming that the in vivo correlative observations we report are mechanistic, rather than hypothesis generating. In some cases, we were able to show a mechanistic relationship between specific genes/pathway and the magnitude of viral infection (Fig. 5) . Importantly, this in vitro model provides a physiologically relevant system to further pursue mechanistic hypotheses resulting from analysis of our in vivo data. However, this model also has limitations in that it currently isolates epithelial cell responses, while our data clearly suggests involvement of leukocytes and monocytes in vivo.