Generation of chimeric respiratory viruses with altered tropism by coinfection of influenza A virus and respiratory syncytial virus

Haney, J., Vijayakrishnan, S. , Streetley, J. , Dee, K., Goldfarb, D. M., Clarke, M. , Mullin, M., Carter, S. D. , Bhella, D. and Murcia, P. R. (2021) Generation of chimeric respiratory viruses with altered tropism by coinfection of influenza A virus and respiratory syncytial virus. bioRxiv, (doi: 10.1101/2021.08.16.456460) (Submitted)

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Abstract

Interactions between co-circulating respiratory viruses are recognized for their impact on viral transmission and clinical outcomes. However, the consequences of these virus-virus interactions at the cellular level are unclear. We coinfected human lung cells with influenza A virus (IAV) and respiratory syncytial virus (RSV). Super-resolution microscopy combined with live-cell imaging and scanning electron microscopy identified extracellular and membrane-associated filamentous structures, likely composed of elements of both IAV and RSV virions. Cryo-electron tomography confirmed the presence of chimeric virus particles exhibiting glycoproteins and ribonucleoproteins of both parental viruses. Functional assays revealed chimeric particles facilitate IAV infection in cells depleted of IAV receptors, demonstrating expanded tropism. Our observations define a previously unknown interaction that is likely to affect virus pathogenesis and have profound implications for infection biology.

Item Type:Articles
Additional Information:This work was supported by grants from the Medical Research Council of the United Kingdom (MC_UU_12014/9 to PRM, MR/N013166/1 to JH, MR/R502327/1 to DMG, MC_UU_12014/7 to SV, and MC_UU_12014/7 to DB). The Scottish Centre for Macromolecular Imaging (SCMI) is funded by the MRC (MC_PC_17135) and SFC (H17007).
Status:Submitted
Refereed:No
Glasgow Author(s) Enlighten ID:Carter, Dr Stephen and Clarke, Dr Mairi and Streetley, Dr James and Haney, Joanne and Mullin, Mrs Margaret and Goldfarb, Daniel Max and Bhella, Professor David and Vijayakrishnan, Dr Swetha and Murcia, Professor Pablo and Dee, Dr Kieran
Authors: Haney, J., Vijayakrishnan, S., Streetley, J., Dee, K., Goldfarb, D. M., Clarke, M., Mullin, M., Carter, S. D., Bhella, D., and Murcia, P. R.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Centre for Virus Research
Journal Name:bioRxiv
Publisher:Cold Spring Harbor Laboratory
Copyright Holders:Copyright © 2021 The Authors
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172630002Respiratory Infections: Epidemiology, evolution and ecology of respiratory viruses (Programme 1)Pablo MurciaMedical Research Council (MRC)MC_UU_12014/9III - Centre for Virus Research
304005MRC Precision Medicine Training GrantMorven BarlassMedical Research Council (MRC)MR/N013166/1-LGH/MS/MED25CAMS - Cardiovascular Science
313949National Productivity Investment Fund StudentshipsGeorge BaillieMedical Research Council (MRC)MR/R502327/1MVLS - Graduate School
172630012Virus Structure (Programme 8)David BhellaMedical Research Council (MRC)MC_UU_12014/7III - Centre for Virus Research
301445The Scottish Macromolecular Imaging Centre (SMIC)David BhellaMedical Research Council (MRC)MC_PC_17135III - Centre for Virus Research
301474The purchase and maintenance of a cryo-electron microscopeDavid BhellaScottish Funding Council (SFC)H17007III - Centre for Virus Research