title: Phenotypic differences in viral immune escape explained by linking within-host dynamics to host-population immunity.
abstract: Viruses that do not cause life-long immunity persist by evolving rapidly in response to prevailing host immunity. The immune-escape mutants emerge frequently, displacing or co-circulating with native strains even though mutations conferring immune evasion are often detrimental to viral replication. The epidemiological dynamics of immune-escape in acute-infection viruses with high transmissibility have been interpreted mainly through immunity dynamics at the host population level, despite the fact that immune-escape evolution involves dynamical processes that feedback across the within- and between-host scales. To address this gap, we use a nested model of within- and between-host infection dynamics to examine how the interaction of viral replication rate and cross-immunity imprint host population immunity, which in turn determines viral immune escape. Our explicit consideration of direct and immune-mediated competitive interactions between strains within-hosts revealed three insights pertaining to risk and control of viral immune-escape: (1) replication rate and immune-stimulation deficiencies (i.e., original antigenic sin) act synergistically to increase immune escape, (2) immune-escape mutants with replication deficiencies relative to their wildtype progenitor are most successful under moderate cross-immunity and frequent re-infections, and (3) the immunity profile along short host-transmission chains (local host-network structure) is a key determinant of immune escape.
authors.affiliation: Department of Biology, Center for Infectious Disease Dynamics, Pennsylvania State University, University Park, PA 16802, USA. kmp29@psu.edu
authors.forename: K M
authors.initials: KM
authors.lastname: Pepin
authors.forename: I
authors.initials: I
authors.lastname: Volkov
authors.forename: J R
authors.initials: JR
authors.lastname: Banavar
authors.forename: C O
authors.initials: CO
authors.lastname: Wilke
authors.forename: B T
authors.initials: BT
authors.lastname: Grenfell
mesh_terms: D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion / Q000276:immunology*; D007109:Immunity / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011157:Population Dynamics; D014777:Virus Diseases / Q000276:immunology / Q000635:transmission; D014779:Virus Replication / Q000276:immunology; D014780:Viruses / Q000276:immunology*