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Phenotypic differences in viral immune escape explained by linking within-host dynamics to host-population immunity

Author(s): Pepin, K.M.; Volkov, I.; Banavar, J.R.; Wilke, C.O.; Grenfell, Bryan T.

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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.
Publication Date: Aug-2010
Citation: Pepin, K.M., Volkov, I., Banavar, J.R., Wilke, C.O., Grenfell, B.T. (2010). Phenotypic differences in viral immune escape explained by linking within-host dynamics to host-population immunity. Journal of Theoretical Biology, 265 (4), 501 - 510. doi:10.1016/j.jtbi.2010.05.036
DOI: doi:10.1016/j.jtbi.2010.05.036
ISSN: 0022-5193
Pages: 501 - 510
Type of Material: Journal Article
Journal/Proceeding Title: Journal of Theoretical Biology
Version: Author's manuscript

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