Phenotypic differences in viral immune escape explained by linking within-host dynamics to host-population immunity.
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.
Pepin
K M
KM
Department of Biology, Center for Infectious Disease Dynamics, Pennsylvania State University, University Park, PA 16802, USA. kmp29@psu.edu
Volkov
I
I
Banavar
J R
JR
Wilke
C O
CO
Grenfell
B T
BT
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*