Journal article

Prior infection with unrelated neurotropic virus exacerbates influenza disease and impairs lung T cell responses

IJH Foo, BY Chua, EB Clemens, SY Chang, X Jia, HA McQuilten, AHY Yap, AF Cabug, M Ashayeripanah, HEG McWilliam, JA Villadangos, M Evrard, LK Mackay, LM Wakim, JK Fazakerley, K Kedzierska, L Kedzierski

Nature Communications | Published : 2024

Abstract

Immunity to infectious diseases is predominantly studied by measuring immune responses towards a single pathogen, although co-infections are common. In-depth mechanisms on how co-infections impact anti-viral immunity are lacking, but are highly relevant to treatment and prevention. We established a mouse model of co-infection with unrelated viruses, influenza A (IAV) and Semliki Forest virus (SFV), causing disease in different organ systems. SFV infection eight days before IAV infection results in prolonged IAV replication, elevated cytokine/chemokine levels and exacerbated lung pathology. This is associated with impaired lung IAV-specific CD8+ T cell responses, stemming from suboptimal CD8+..

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Grants

Awarded by University of Melbourne grant


Awarded by NHMRC Leadership Investigator Grant


Awarded by NHMRC


Awarded by Melbourne Research Scholarship


Funding Acknowledgements

We acknowledge the Melbourne Cytometry Platform (The Doherty Institute) for provision of flow cytometry services and Phenomics Australia Histopathology and Digital Slide Service at the University of Melbourne for the histopathological assessments. We would like to thank Melbourne Bioresources Platform staff at the Doherty Institute. The work was funded by a University of Melbourne grant to J.K.F., the NHMRC Leadership Investigator Grant to K.K. (#1173871) and J.A.V. (#2016969), an NHMRC Project Grant (#1163090) and an NHMRC Principal Research Fellowship (#1154502) to J.A.V.; I.J.H.F. is a recipient of the Melbourne Research Scholarship. X.J. was a recipient of the China Scholarship Council-UoM Joint Scholarship. K.K. is NHMRC L1 Investigator Fellow (#1173871) and University of Melbourne Dame Kate Campbell Fellow, EBC is NHMRC Peter Doherty Fellow (#1091516), J.A.V. is NHMRC L3 Investigator Fellow.