Pathogen evolution and the immunological niche

Cobey, Sarah

doi:10.1111/nyas.12493

Cited by 65 publications

(53 citation statements)

References 168 publications

(306 reference statements)

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“…Antigenic distances are typically measured using sera isolated from ferrets recovering from influenza virus infections [45]. With epitope-specific immunity, the antigenic distance between two strains can differ among hosts with different immune histories (Figure 1B,C) [46,47]. Thus, strains that appear antigenically similar according to antibodies raised in ferrets (i.e., in animals without prior influenza virus exposures) might be distinct from antibodies in adults [36].…”

Section: Implications For Viral Evolution and Vaccinationmentioning

confidence: 99%

Immune history and influenza virus susceptibility

Cobey

Hensley

2017

Current Opinion in Virology

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Antibody responses to influenza viruses are critical for protection, but the ways in which repeated viral exposures shape antibody evolution and effectiveness over time remain controversial. Early observations demonstrated that the history of viral exposures has a profound effect on the specificity and magnitude of antibody responses to a new viral strain, a phenomenon called “original antigenic sin.” Although “sin” might suppress some aspects of the immune response, so far there is little indication that hosts with pre-existing immunity are more susceptible to viral infections compared to naïve hosts. However, the tendency of the immune response to focus on previously recognized conserved epitopes when encountering new viral strains can create an opportunity cost when mutations arise in these conserved epitopes. Hosts with different exposure histories may continue to experience distinct patterns of infection over time, which may influence influenza viruses’ continued antigenic evolution. Understanding the dynamics of B cell competition that underlie the development of antibody responses might help explain the low effectiveness of current influenza vaccines and lead to better vaccination strategies.

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Section: Implications For Viral Evolution and Vaccinationmentioning

confidence: 99%

Immune history and influenza virus susceptibility

Cobey

Hensley

2017

Current Opinion in Virology

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222

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“…In more general terms, this paper brings support to the view that understanding pathogen evolution requires abandoning the simple SIR paradigm for more complex models of host-pathogen interaction 41 and is also a first step toward a comprehensive computational modeling platform where such models can be tested for realistic population sizes on a desktop computer. The modular structure of the code built for the present work allows changing some assumptions, such as the host's immunity buildup and response and the form of the cross-immunity function, through easy adaptations.…”

Section: Discussionmentioning

confidence: 91%

Host immunity and pathogen diversity: A computational study

Aquino

Nunes

2016

Virulence

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The distinctive features of human influenza A phylogeny have inspired many mathematical and computational studies of viral infections spreading in a host population, but our understanding of the mechanisms that shape the coupled evolution of host immunity, disease incidence and viral antigenic properties is far from complete. In this paper we explore the epidemiology and the phylogeny of a rapidly mutating pathogen in a host population with a weak immune response, that allows re-infection by the same strain and provides little cross-immunity. We find that mutation generates explosive diversity and that, as diversity grows, the system is driven to a very high prevalence level. This is in stark contrast with the behavior of similar models where mutation gives rise to a large epidemic followed by disease extinction, under the assumption that infection with a strain provides lifelong immunity. For low mutation rates, the behavior of the system shows the main qualitative features of influenza evolution. Our results highlight the importance of heterogeneity in the human immune response for understanding influenza A phenomenology. They are meant as a first step toward computationally affordable, individual based models including more complex host-pathogen interactions.

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“…The 'immunological niche' concept states that, due to the diversity and complexity of immune responses, 79 every individual host represents a unique habitat that requires adaptation (Cobey 2014). Considering that 80 the pathogen needs to adapt to every new host, the host population taken as a whole represents an 81 extremely heterogeneous environment where adaptive processes are ongoing and persistence of 82 mutator alleles may be favoured (Lukacisinova, et al 2017).…”

Section: Introduction 36mentioning

confidence: 99%

Evolutionary epidemiology ofStreptococcus iniae: linking mutation rate dynamics with adaptation to novel immunological landscapes

Silayeva

Engelstädter

Barnes

2018

Preprint

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Pathogens continuously adapt to changing host environments where variation in their virulence and antigenicity is critical to their long-term evolutionary success. The emergence of novel variants is accelerated in microbial mutator strains (mutators) deficient in DNA repair genes, most often from mismatch repair and oxidised-guanine repair systems (MMR and OG respectively). Bacterial MMR/OG mutants are abundant in clinical samples and show increased adaptive potential in experimental infection models, yet the role of mutators in the epidemiology and evolution of infectious disease is not well understood. Here we investigated the role of mutation rate dynamics in the evolution of a broad host range pathogen, Streptococcus iniae, using a set of 80 strains isolated globally over 40 years. We have resolved phylogenetic relationships using non-recombinant core genome variants, measured in vivo mutation rates by fluctuation analysis, identified variation in major MMR/OG genes and their regulatory regions, and phenotyped the major traits determining virulence in streptococci. We found that both mutation rate and MMR/OG genotype are remarkably conserved within phylogenetic clades but significantly differ between major phylogenetic lineages. Further, variation in MMR/OG loci correlates with occurrence of atypical virulence-associated phenotypes, infection in atypical hosts (mammals), and atypical tissue of a vaccinated primary hosts (barramundi bone). These findings suggest that mutators are likely to facilitate adaptations preceding major diversification events, and may promote emergence of variation permitting colonisation of a novel host tissue, novel host taxa (host jumps), and immune-escape in the vaccinated host.

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Pathogen evolution and the immunological niche

Cited by 65 publications

References 168 publications

Immune history and influenza virus susceptibility

Immune history and influenza virus susceptibility

Host immunity and pathogen diversity: A computational study

Evolutionary epidemiology ofStreptococcus iniae: linking mutation rate dynamics with adaptation to novel immunological landscapes

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