Abstract
Respiratory syncytial virus strains differentially activate the inflammasome eliciting a pathogenic Th17 response
The Journal of immunology (1950), Vol.202(1_Supplement), pp.198-198.3
05/01/2019
DOI: 10.4049/jimmunol.202.Supp.198.3
Abstract
Abstract Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in young children worldwide with no licensed vaccine available. RSV-induced disease ranges from mild to severe, with severe disease correlated with elevated levels of pro-inflammatory cytokines, including the Th17-associated cytokine IL-17. To better understand the virus factors that influence the induction of a Th17 response, we compared the inflammatory responses elicited by different RSV strains. In contrast to the commonly used RSV A2 strain, RSV 2–20 infection resulted in increased levels of IL-6 and IL-1β, which were required to induce a pathogenic Th17 response. Th17 induction was associated with increased mucus production and airway hyperreactivity following RSV 2–20 infection indicating a strain-dependent increase in disease severity. A recombinant RSV A2 virus expressing the 2–20 fusion (F) protein induced IL-1β to similar levels as wild-type RSV 2–20 suggesting that the 2–20 F protein is necessary for increased pro-inflammatory cytokine production. Sequencing of the RSV A2 and 2–20 F protein genes revealed three point mutations in a region likely to interact with host cells. Reversion of these three amino acids in the RSV A2/2–20 F recombinant virus to the A2 sequence significantly reduced RSV-induced IL-6 and IL-1β protein production. Together our results demonstrate that the RSV F protein plays an essential role in the induction of pro-inflammatory cytokines which are critical for CD4 Th17 cell differentiation. Genetic variations in the RSV F protein between RSV strains play a crucial role in modulating RSV-induced disease severity in the animal model and may contribute to the differential RSV pathogenesis observed in humans.
Details
- Title: Subtitle
- Respiratory syncytial virus strains differentially activate the inflammasome eliciting a pathogenic Th17 response
- Creators
- Kody Waldstein - University of IowaKayla A. Weiss - University of IowaStacey Hartwig - University of IowaHannah Quick - University of IowaBarun Poudel - University of IowaPrajwal Gurung - University of IowaSteven M Varga - University of Iowa
- Resource Type
- Abstract
- Publication Details
- The Journal of immunology (1950), Vol.202(1_Supplement), pp.198-198.3
- DOI
- 10.4049/jimmunol.202.Supp.198.3
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Language
- English
- Date published
- 05/01/2019
- Academic Unit
- Microbiology and Immunology; Infectious Diseases; Internal Medicine; Otolaryngology; Stead Family Department of Pediatrics
- Record Identifier
- 9984362340402771
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