Journal
JOURNAL OF THEORETICAL BIOLOGY
Volume 265, Issue 4, Pages 501-510Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jtbi.2010.05.036
Keywords
Cross-immunity; Within-host dynamics; Original antigenic sin; Adaptive immunity; Competition
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Funding
- NSF [EF-0742373]
- NIH [R01 GM083983-01]
- Science & Technology Directorate, Department of Homeland Security
- Fogarty International Center, National Institutes of Health
- Direct For Biological Sciences
- Emerging Frontiers [1160765, 742373] Funding Source: National Science Foundation
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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. (C) 2010 Elsevier Ltd. All rights reserved.
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