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.
Influenza viruses can interact during coinfections, allowing viral fitness to be altered by genome complementation and competition, and increasing population diversity through reassortment. However, opportunities for these interactions are limited, as coinfection is blocked shortly after primary infection by a process known as superinfection exclusion (SIE). We asked whether SIE, which occurs at the level of individual cells, could limit within-host interactions between populations of influenza viruses as they spread across regions of cells. We first created a simplified model of within-host spread by infecting monolayers of cells with two isogenic influenza A viruses, each encoding a different fluorophore, and measuring the proportion of coinfected cells. In this system SIE begins within 2-4 hours of primary infection, with the kinetics of onset defined by the dose of primary virus. We then asked how SIE controls opportunities for coinfection as viruses spread across a monolayer of cells. We observed that viruses spreading from a single coinfected focus continued to coinfect cells as they spread, as 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 SIE blocked further coinfection. This patterning was recapitulated in the lungs of infected mice and is likely to apply to other viruses that exhibit SIE. It suggests that the kinetics of SIE onset separate a spreading infection into discrete regions, within which interactions between virus populations can occur freely, and between which they are blocked.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.