title: Host immunity and pathogen diversity: A computational study.
abstract: 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.
authors.affiliation: a Department of Civil & Environmental Engineering and Earth Sciences ; University of Notre Dame ; Notre Dame , IN USA.
authors.forename: Tomás
authors.initials: T
authors.lastname: Aquino
authors.affiliation: b BioISI Biosystems & Integrative Sciences Institute and Departamento de Física; Faculdade de Ciências da Universidade de Lisboa ; Lisboa , Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Nunes
mesh_terms: D019295:Computational Biology; D019143:Evolution, Molecular; D014644:Genetic Variation; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology*; D007251:Influenza, Human / Q000453:epidemiology / Q000276:immunology / Q000821:virology*; D008954:Models, Biological; D008962:Models, Theoretical; D009154:Mutation; D010802:Phylogeny; D011157:Population Dynamics
keywords: individual-based models; influenza A; reinfection threshold; strain competition and evolution
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