Superinfection exclusion: A viral strategy with short-term benefits and long-term drawbacks

Hunter, Michael; Fusco, Diana

doi:10.1371/journal.pcbi.1010125

Cited by 28 publications

(20 citation statements)

References 68 publications

(99 reference statements)

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“…Namely, it allows the semi-infectious progeny virions which make up the majority of the viral population (10) to complement each other. Coinfection allows these otherwise "non-infectious" virus particles to contribute to productive infections (44,45).Stochastic simulations in bacteriophage have demonstrated that viral populations that are incapable of initiating SIE are more able to fix beneficial mutations (46). Therefore, unrestricted coinfection between the progeny of a virus could help to maintain viral population fitness.…”

Section: Discussionmentioning

confidence: 99%

Superinfection exclusion creates spatially distinct influenza virus populations

Sims

Tornaletti

Jasim

et al. 2022

Preprint

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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.

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Section: Discussionmentioning

confidence: 99%

Superinfection exclusion creates spatially distinct influenza virus populations

Sims

Tornaletti

Jasim

et al. 2022

Preprint

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“…Waning immunity has been included previously in a range of epidemiological models (62,63), and is a target for future addition to the modelling framework presented here, along with consideration of heterogeneity in immunity between previously infected hosts. Additionally, similar investigations to those conducted here could be undertaken for scenarios in which multiple viruses are co-circulating (potentially allowing for superinfection (64)). This could include analyses of epidemiological dynamics beyond the early phase of the outbreak of the novel variant, after it has invaded the host population.…”

Section: Discussionmentioning

confidence: 96%

The impact of cross-reactive immunity on the emergence of SARS-CoV-2 variants

Thompson

Southall²,

Daon³

et al. 2023

Front. Immunol.

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IntroductionA key feature of the COVID-19 pandemic has been the emergence of SARS-CoV-2 variants with different transmission characteristics. However, when a novel variant arrives in a host population, it will not necessarily lead to many cases. Instead, it may fade out, due to stochastic effects and the level of immunity in the population. Immunity against novel SARS-CoV-2 variants may be influenced by prior exposures to related viruses, such as other SARS-CoV-2 variants and seasonal coronaviruses, and the level of cross-reactive immunity conferred by those exposures.MethodsHere, we investigate the impact of cross-reactive immunity on the emergence of SARS-CoV-2 variants in a simplified scenario in which a novel SARS-CoV-2 variant is introduced after an antigenically related virus has spread in the population. We use mathematical modelling to explore the risk that the novel variant invades the population and causes a large number of cases, as opposed to fading out with few cases.ResultsWe find that, if cross-reactive immunity is complete (i.e. someone infected by the previously circulating virus is not susceptible to the novel variant), the novel variant must be more transmissible than the previous virus to invade the population. However, in a more realistic scenario in which cross-reactive immunity is partial, we show that it is possible for novel variants to invade, even if they are less transmissible than previously circulating viruses. This is because partial cross-reactive immunity effectively increases the pool of susceptible hosts that are available to the novel variant compared to complete cross-reactive immunity. Furthermore, if previous infection with the antigenically related virus assists the establishment of infection with the novel variant, as has been proposed following some experimental studies, then even variants with very limited transmissibility are able to invade the host population.DiscussionOur results highlight that fast assessment of the level of cross-reactive immunity conferred by related viruses against novel SARS-CoV-2 variants is an essential component of novel variant risk assessments.

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“…For IAV, genome complementation within an infected lesion would mean that the semi-infectious progeny virions that make up around 90% the viral population could contribute to productive infection [ 44 – 46 ]. In a similar way, stochastic simulations of the effects of SIE in bacteriophage have demonstrated that viral populations that are incapable of initiating SIE would be less able to fix beneficial mutations [ 47 ]. We suggest that for IAV coinfection between the progeny of a virus could help to maintain viral population fitness.…”

Section: Discussionmentioning

confidence: 99%

Superinfection exclusion creates spatially distinct influenza virus populations

et al. 2023

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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.

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Superinfection exclusion: A viral strategy with short-term benefits and long-term drawbacks

Cited by 28 publications

References 68 publications

Superinfection exclusion creates spatially distinct influenza virus populations

Superinfection exclusion creates spatially distinct influenza virus populations

The impact of cross-reactive immunity on the emergence of SARS-CoV-2 variants

Superinfection exclusion creates spatially distinct influenza virus populations

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