Superinfection exclusion creates spatially distinct influenza virus populations

Sims, A. et al. (2023) Superinfection exclusion creates spatially distinct influenza virus populations. PLoS Biology, 21(2), e3001941. (doi: 10.1371/journal.pbio.3001941) (PMID:36757937) (PMCID:PMC9910727)

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Interactions between viruses during coinfections can influence viral fitness and population diversity, as seen in the generation of reassortant pandemic influenza A virus (IAV) strains. However, opportunities for interactions between closely related viruses are limited by a process known as superinfection exclusion (SIE), which blocks coinfection shortly after primary infection. Using IAVs, we asked whether SIE, an effect which occurs at the level of individual cells, could limit interactions between populations of viruses as they spread across multiple cells within a host. To address this, we first measured the kinetics of SIE in individual cells by infecting them sequentially with 2 isogenic IAVs, each encoding a different fluorophore. By varying the interval between addition of the 2 IAVs, we showed that early in infection SIE does not prevent coinfection, but that after this initial lag phase the potential for coinfection decreases exponentially. We then asked how the kinetics of SIE onset controlled coinfections as IAVs spread asynchronously across monolayers of cells. We observed that viruses at individual coinfected foci continued to coinfect cells as they spread, because all new infections were of cells that had not yet established SIE. In contrast, viruses spreading towards each other from separately infected foci could only establish minimal regions of coinfection before reaching cells where coinfection was blocked. This created a pattern of separate foci of infection, which was recapitulated in the lungs of infected mice, and which is likely to be applicable to many other viruses that induce SIE. We conclude that the kinetics of SIE onset segregate spreading viral infections into discrete regions, within which interactions between virus populations can occur freely, and between which they are blocked.

Item Type:Articles
Additional Information:The authors acknowledge funding from the UK Medical Research Council (MRC), as studentships to A.S., J.H. and J.W. [MC_ST_CVR_2019], as CVR core funding to C.B. [MC_UU_12014/5] and as a Career Development Award and Transition Support Award to E.H. [MR/N008618/1 and MR/V035789/1]; funding from the University of Glasgow to E.H., and funding from Cancer Research UK (CRUK) to E.R. [A_BICR_1920_Roberts].
Glasgow Author(s) Enlighten ID:Jasim, Dr Seema and Wojtus, Ms Joanna and Loney, Mr Colin and Hutchinson, Dr Edward and Roberts, Dr Ed and Sims, Anna and Hirst, Jack and Boutell, Dr Chris and Devlin, Ryan and Sloan, Dr Elizabeth
Creator Roles:
Sims, A.Conceptualization, Investigation, Methodology, Visualization, Writing – original draft, Writing – review and editing
Jasim, S.Conceptualization, Investigation, Methodology, Visualization
Devlin, R.Investigation, Methodology
Hirst, J. C.Conceptualization, Methodology, Visualization
Loney, C.Methodology, Visualization
Wojtus, J.Conceptualization, Methodology
Sloan, E.Conceptualization, Methodology
Boutell, C.Funding acquisition, Supervision
Roberts, E.Funding acquisition, Investigation, Methodology, Visualization
Hutchinson, E.Conceptualization, Funding acquisition, Methodology, Supervision, Writing – review and editing
Authors: Sims, A., Tornaletti, L. B., Jasim, S., Pirillo, C., Devlin, R., Hirst, J. C., Loney, C., Wojtus, J., Sloan, E., Thorley, L., Boutell, C., Roberts, E., and Hutchinson, E.
College/School:College of Medical Veterinary and Life Sciences > School of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:PLoS Biology
Publisher:Public Library of Science
Published Online:09 February 2023
Copyright Holders:Copyright © 2023 Sims et al.
First Published:First published in PLoS Biology 21(2): e3001941
Publisher Policy:Reproduced under a Creative Commons License
Related URLs:
Data DOI:10.5525/gla.researchdata.1370

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