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{Penn:2022:10.1128/jvi.01178-22,
author = {Penn, R and Tregoning, J and Flight, K and Frise, R and Baillon, L and Goldhill, D and Johansson, C and Barclay, W},
doi = {10.1128/jvi.01178-22},
journal = {Journal of Virology},
pages = {1--18},
title = {Levels of Influenza defective viral genomes determine pathogenesis in the BALB/c mouse model},
url = {http://dx.doi.org/10.1128/jvi.01178-22},
volume = {96},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Defective viral genomes (DVGs), which are generated by the viral polymerase in error during RNA replication, can trigger innate immunity and are implicated in altering the clinical outcome of infection. Here, we investigated the impact of DVGs on innate immunity and pathogenicity in a BALB/c mouse model of influenza virus infection. We generated stocks of influenza viruses containing the internal genes of an H5N1 virus that contain different levels of DVGs (indicated by different genome to PFU ratios). In lung epithelial cells, the high DVG stock was immunostimulatory at early time points post infection. DVGs were amplified during virus replication in myeloid immune cells and triggered pro-inflammatory cytokine production. In the mouse model, infection with the different virus stocks produced divergent outcomes. The high DVG stock induced an early type I IFN resonse that limited viral replication in the lungs resulting in minimal weight loss. In contrast, the virus stock with low levels of DVGs replicated to hightitres and amplified DVGs over time resulting in elevated pro-inflammatory cytokines accompanied by rapid weight loss and increased morbidity and mortality. Our results suggest that the timing and levels of  immunostimulatory DVGs generated duringinfection contribute to H5N1 pathogenesis.
AU  - Penn,R
AU  - Tregoning,J
AU  - Flight,K
AU  - Frise,R
AU  - Baillon,L
AU  - Goldhill,D
AU  - Johansson,C
AU  - Barclay,W
DO  - 10.1128/jvi.01178-22
EP  - 18
PY  - 2022///
SN  - 0022-538X
SP  - 1
TI  - Levels of Influenza defective viral genomes determine pathogenesis in the BALB/c mouse model
T2  - Journal of Virology
UR  - http://dx.doi.org/10.1128/jvi.01178-22
UR  - https://journals.asm.org/doi/10.1128/jvi.01178-22
UR  - http://hdl.handle.net/10044/1/100062
VL  - 96
ER  -
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