Imperial College London
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Dr John S Tregoning

Faculty of Medicine, Department of Infectious Disease

Professor in Vaccine Immunology
 
 
 
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Contact

 

john.tregoning Website

 
 
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Location

 

456 (Shattock Group)Wright Fleming WingSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Russell:2015:10.1128/JVI.01070-15,
author = {Russell, RF and McDonald, JU and Ivanova, M and Zhong, Z and Bukreyev, A and Tregoning, JS},
doi = {10.1128/JVI.01070-15},
journal = {Journal of Virology},
pages = {8974--8981},
title = {Partialattenuation of respiratory syncytial virus with a deletion of a small hydrophobic gene Is associated with elevated interleukin-1β responses},
url = {http://dx.doi.org/10.1128/JVI.01070-15},
volume = {89},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - The small hydrophobic (SH) gene of respiratory syncytial virus (RSV), a major cause of infant hospitalization, encodes a viroporin of unknown function. SH gene knockout virus (RSV ΔSH) is partially attenuated in vivo, but not in vitro, suggesting that the SH protein may have an immunomodulatory role. RSV ΔSH has been tested as a live attenuated vaccine in humans and cattle, and here we demonstrate that it protected against viral rechallenge in mice. We compared the immune response to infection with RSV wild type and RSV ΔSH in vivo using BALB/c mice and in vitro using epithelial cells, neutrophils, and macrophages. Strikingly, the interleukin-1β (IL-1β) response to RSV ΔSH infection was greater than to wild-type RSV, in spite of a decreased viral load, and when IL-1β was blocked in vivo, the viral load returned to wild-type levels. A significantly greater IL-1β response to RSV ΔSH was also detected in vitro, with higher-magnitude responses in neutrophils and macrophages than in epithelial cells. Depleting macrophages (with clodronate liposome) and neutrophils (with anti-Ly6G/1A8) demonstrated the contribution of these cells to the IL-1β response in vivo, the first demonstration of neutrophilic IL-1β production in response to viral lung infection. In this study, we describe an increased IL-1β response to RSV ΔSH, which may explain the attenuation in vivo and supports targeting the SH gene in live attenuated vaccines.
AU  - Russell,RF
AU  - McDonald,JU
AU  - Ivanova,M
AU  - Zhong,Z
AU  - Bukreyev,A
AU  - Tregoning,JS
DO  - 10.1128/JVI.01070-15
EP  - 8981
PY  - 2015///
SN  - 1098-5514
SP  - 8974
TI  - Partialattenuation of respiratory syncytial virus with a deletion of a small hydrophobic gene Is associated with elevated interleukin-1β responses
T2  - Journal of Virology
UR  - http://dx.doi.org/10.1128/JVI.01070-15
UR  - http://hdl.handle.net/10044/1/33118
VL  - 89
ER  -
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