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- Lien Anh Ha Do, Johann Pellet, H Rogier van Doorn, Anh Tuan Tran, Bach Hue Nguyen, Thi Thu Loan Tran, Quynh Huong Tran, Quoc Bao Vo, Nguyen Anh Tran Dac, Hong Nhien Trinh, Thi Thanh Hai Nguyen, Bao Tinh Le Binh, Huu Mai Khanh Nguyen, Minh Tien Nguyen, Quang Tung Thai, Thanh Vu Vo, Ngoc Quang Minh Ngo, Thi Kim Huyen Dang, Ngoc Huong Cao, Thu Van Tran, Lu Viet Ho, Bertrand De Meulder, Charles Auffray, Jorrit-Jan Hofstra, Jeremy Farrar, Juliet E Bryant, Menno de Jong, and Martin L Hibberd.
- Oxford University Clinical Research Unit, Wellcome Trust Major Overseas Program, in partnership with the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
- J. Infect. Dis. 2017 Dec 27; 217 (1): 134-146.
BackgroundMost insights into the cascade of immune events after acute respiratory syncytial virus (RSV) infection have been obtained from animal experiments or in vitro models.MethodsIn this study, we investigated host gene expression profiles in nasopharyngeal (NP) swabs and whole blood samples during natural RSV and rhinovirus (hRV) infection (acute versus early recovery phase) in 83 hospitalized patients <2 years old with lower respiratory tract infections.ResultsRespiratory syncytial virus infection induced strong and persistent innate immune responses including interferon signaling and pathways related to chemokine/cytokine signaling in both compartments. Interferon-α/β, 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 swab and blood specimens. In contrast, hRV infection did not as strongly induce expression of innate immunity pathways, and significant differences were observed between NP swab and blood specimens.ConclusionsWe 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.© The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America.
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