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

JOURNAL OF THEORETICAL BIOLOGY

卷:265

Article

Pepin, K. M.^1,2  Volkov, I.²  Banavar, J. R.²  Wilke, C. O.^3,4  Grenfell, B. T.^5,6 

[1] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA

[2] Penn State Univ, Dept Phys, University Pk, PA 16802 USA

[3] Univ Texas Austin, Ctr Computat Biol & Bioinformat, Inst Cell & Mol Biol, Austin, TX 78712 USA

[4] Univ Texas Austin, Sect Integrat Biol, Austin, TX 78712 USA

[5] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA

[6] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA

关键词: Cross-immunity;    Within-host dynamics;    Original antigenic sin;    Adaptive immunity;    Competition;   

DOI  :  10.1016/j.jtbi.2010.05.036

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

Free