A general framework for modelling the impact of co-infections on pathogen evolution

Bushman, Mary; Antia, Rustom

doi:10.1098/rsif.2019.0165

Cited by 10 publications

(8 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it may also be the case that a mutation has a disproportionate effect on intracellular viral fitness. Future work should therefore examine the impact of a mutation’s ‘dominance’ [ 32 ] on in vivo viral evolution.…”

Section: Discussionmentioning

confidence: 99%

Fitness Estimation for Viral Variants in the Context of Cellular Coinfection

Zhu

Allman

Koelle

2021

Viruses

View full text Add to dashboard Cite

Animal models are frequently used to characterize the within-host dynamics of emerging zoonotic viruses. More recent studies have also deep-sequenced longitudinal viral samples originating from experimental challenges to gain a better understanding of how these viruses may evolve in vivo and between transmission events. These studies have often identified nucleotide variants that can replicate more efficiently within hosts and also transmit more effectively between hosts. Quantifying the degree to which a mutation impacts viral fitness within a host can improve identification of variants that are of particular epidemiological concern and our ability to anticipate viral adaptation at the population level. While methods have been developed to quantify the fitness effects of mutations using observed changes in allele frequencies over the course of a host’s infection, none of the existing methods account for the possibility of cellular coinfection. Here, we develop mathematical models to project variant allele frequency changes in the context of cellular coinfection and, further, integrate these models with statistical inference approaches to demonstrate how variant fitness can be estimated alongside cellular multiplicity of infection. We apply our approaches to empirical longitudinally sampled H5N1 sequence data from ferrets. Our results indicate that previous studies may have significantly underestimated the within-host fitness advantage of viral variants. These findings underscore the importance of considering the process of cellular coinfection when studying within-host viral evolutionary dynamics.

show abstract

Section: Discussionmentioning

confidence: 99%

Fitness Estimation for Viral Variants in the Context of Cellular Coinfection

Zhu

Allman

Koelle

2021

Viruses

View full text Add to dashboard Cite

show abstract

“…However, it may also be the case that a mutation has a disproportionate effect on intracellular viral fitness. Future work should therefore examine the impact of a mutation's 'dominance' [30] on in vivo viral evolution.…”

Section: Discussionmentioning

confidence: 99%

Fitness estimation for viral variants in the context of cellular coinfection

Zhu

Allman

Koelle

2021

Preprint

View full text Add to dashboard Cite

Animal models are frequently used to characterize the within-host dynamics of emerging zoonotic viruses. More recent studies have also deep-sequenced longitudinal viral samples originating from experimental challenges to gain a better understanding of how these viruses may evolve in vivo and between transmission events. These studies have often identified nucleotide variants that can replicate more efficiently within hosts and also transmit more effectively between hosts. Quantifying the degree to which a mutation impacts viral fitness within a host can improve identification of variants that are of particular epidemiological concern and our ability to anticipate viral adaptation at the population level. While methods have been developed to quantify the fitness effects of mutations using observed changes in allele frequencies over the course of a host’s infection, none of the existing methods account for the possibility of cellular coinfection. Here, we develop mathematical models to project variant allele frequency changes in the context of cellular coinfection and, further, integrate these models with statistical inference approaches to demonstrate how variant fitness can be estimated alongside cellular multiplicity of infection. We apply our approaches to empirical longitudinally-sampled H5N1 sequence data from ferrets. Our results indicate that previous studies may have significantly underestimated the within-host fitness advantage of viral variants. These findings underscore the importance of considering the process of cellular coinfection when studying within-host viral evolutionary dynamics.

show abstract

“…Our model agrees that in the face of a growth-transmission trade-off, transmission mutants have the greatest chance of establishing new infections under a tight transmission bottleneck that allows them to avoid competition during colonization, but predicts that competitive exclusion may promote selection for transmission even in respiratory pathogens like IAV and S. pneumoniae . More recent theory has investigated the influence of transmission bottlenecks on the evolution of an emerging pathogen, specifically with R 0 < 1, and the probability that a mutation prevents its extinction in the human population [23, 24]. These models, like ours, find that tight transmission bottlenecks can aid selection for transmissibility through a founder effect, and that wide bottlenecks can prevent the emergence of mutations that improve transmissibility at the expense of within-host fitness, even if they improve R 0 .…”

Section: Discussionmentioning

confidence: 99%

Competitive exclusion strengthens selection for transmissibility and increases the benefit of recombination for within-host adaptation

Jacobs

Weiser

2020

Preprint

View full text Add to dashboard Cite

10Pathogens experience selection at multiple scales, given the need to transmit between hosts 11 and replicate within them. This presents the challenge of cross-scale selective conflict when 12 adaptations to one scale compromise fitness at another, such as mutations that improve 13 transmissibility but make individuals less competitive within hosts. Selection operates differently 14 at these scales, with tight transmission bottlenecks subjecting pathogen populations to genetic drift, 15 and large population sizes within hosts enabling efficient selection for beneficial mutations.16 Compounding the reduction in diversity by transmission bottlenecks is the occupant-intruder 17 competitive strategy exhibited by some pathogens, where the first variant to colonize a host 18 prevents later arriving variants from contributing to infection, preventing immigration and turning 19 transmission into a "founder takes all" contest. Here, we used multiple modeling approaches to 20 examine how this behavior affects the efficiency of selection for both transmissibility and within-21 host fitness. We find that in the face of a trade-off, selection for transmissibility is maximized 22 under a tight transmission bottleneck that minimizes within-host competition during colonization. 23 While mutations with increased within-host fitness are favored during within-host replication, an 24 occupant-intruder strategy prevents these mutants from displacing established residents and 25 propagating across the host population, leading to their extinction if they are insufficiently 26 transmissible. Finally, a model of competition on the scale of the host population revealed that 27 competitive exclusion limits the propagation of mutations with improved within-host fitness, 28 unless resident populations can incorporate alleles from intruding variants by recombination. Thus, 29 competitive exclusion may facilitate the improvement and maintenance of pathogen 30 transmissibility, with directional recombination allowing resident populations to mitigate the 31 potential loss of within-host fitness imposed by this occupant-intruder strategy. 32 Author Summary 33 Transmission is a defining feature of infectious diseases, and so a better understanding of how 34 transmissibility evolves is important for improving disease surveillance and prevention. Successful 35 transmission is often achieved by a small number of individuals which, after establishing residency 36 in a host, may prevent newcomers from participating in infection. Here, we use modeling to 37 examine how competitive exclusion of challengers by resident populations affects the balance 38 between within-host competitive ability and transmissibility. We find that competitive exclusion 39 strengthens selection for transmissibility by disproportionately benefitting the first variant to 40 colonize a host and preventing mutants that may be more competitive but less transmissible from 41 displacing established residents. Competitive exclusion also limits the propagation of mutants that 42 impro...

show abstract

A general framework for modelling the impact of co-infections on pathogen evolution

Cited by 10 publications

References 37 publications

Fitness Estimation for Viral Variants in the Context of Cellular Coinfection

Fitness Estimation for Viral Variants in the Context of Cellular Coinfection

Fitness estimation for viral variants in the context of cellular coinfection

Competitive exclusion strengthens selection for transmissibility and increases the benefit of recombination for within-host adaptation

Contact Info

Product

Resources

About