Host Transcription Profile In Nasal Epithelium And Whole Blood of Hospitalised Children under two years of age with Respiratory Syncytial Virus Infection.

5 years ago

Host Transcription Profile In Nasal Epithelium And Whole Blood of Hospitalised Children under two years of age with Respiratory Syncytial Virus Infection.

Tran Dac, de Jong, Le Binh, Ngo, van Doorn, Auffray, Thai, Bryant, Ho, Trinh, Hibberd, Farrar, Nguyen, Dang, Cao, Pellet, Hofstra, Do, Vo, Vo, Tran, De Meulder

Most insights into the cascade of immune events following acute respiratory syncytial virus (RSV) infection have been obtained from animal experiments or in vitro models. Here we investigated host gene expression profiles in nasopharyngeal swabs (NP) and whole blood samples during natural RSV and rhinovirus (hRV) infection (acute versus early recovery phase) in 83 hospitalised patients <2 years old with lower respiratory tract infections (LRTI). RSV infection induced strong and persistent innate immune responses including interferon signaling and pathways related to chemokine/cytokine signaling in both compartments. Interferon alpha/beta, NOTCH1 signaling pathways and potential biomarkers HIST1H4E, IL7R, ISG15 in NP samples, or BCL6, HIST2H2AC, CCNA1 in blood are leading pathways and hub genes that were associated with both RSV load and severity. The observed RSV-induced gene expression patterns did not differ significantly in NP and blood specimens. In contrast, hRV infection did not as strongly induce expression of innate immunity pathways, and significant differences were observed between NP and blood specimens. We conclude that RSV induced strong and persistent innate immune responses and that RSV severity may be related to development of T follicular helper cells and antiviral inflammatory sequelae derived from high activation of BCL6.

Publisher URL: http://doi.org/10.1093/infdis/jix519

DOI: 10.1093/infdis/jix519