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Updated: Jun 12, 2026

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Phenotypic differences in viral immune escape explained by linking within-host dynamics to host-population immunity
K M Pepin1, I Volkov, J R Banavar
1Department of Biology, Center for Infectious Disease Dynamics, Pennsylvania State University, University Park, PA 16802, USA. kmp29@psu.edu
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.
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