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Phenotypic mixing and hiding may contribute to memory in viral quasispecies

Wilke, Claus O. and Novella, Isabel S. (2003) Phenotypic mixing and hiding may contribute to memory in viral quasispecies. BMC Microbiology, 3 . Art. No. 11. ISSN 1471-2180. PMCID PMC165440. doi:10.1186/1471-2180-3-11.

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Background: In a number of recent experiments with food-and-mouth disease virus, a deleterious mutant, RED, was found to avoid extinction and remain in the population for long periods of time. Since RED characterizes the past evolutionary history of the population, this observation was called quasispecies memory. While the quasispecies theory predicts the existence of these memory genomes, there is a disagreement between the expected and observed mutant frequency values. Therefore, the origin of quasispecies memory is not fully understood. Results: We propose and analyze a simple model of complementation between the wild type virus and a mutant that has an impaired ability of cell entry, the likely cause of fitness differences between wild type and RED mutants. The mutant will go extinct unless it is recreated from the wild type through mutations. However, under phenotypic mixing-and-hiding as a mechanism of complementation, the time to extinction in the absence of mutations increases with increasing multiplicity of infection (m.o.i.). If the RED mutant is constantly recreated by mutations, then its frequency at equilibrium under selection-mutation balance also increases with increasing m.o.i. At high m.o.i., a large fraction of mutant genomes are encapsidated with wild-type protein, which enables them to infect cells as efficiently as the wild type virions, and thus increases their fitness to the wild-type level. Moreover, even at low m.o.i. the equilibrium frequency of the mutant is higher than predicted by the standard quasispecies model, because a fraction of mutant virions generated from wild-type parents will also be encapsidated by wild-type protein. Conclusions: Our model predicts that phenotypic hiding will strongly influence the population dynamics of viruses, particularly at high m.o.i., and will also have important effects on the mutation-selection balance at low m.o.i. The delay in mutant extinction and increase in mutant frequencies at equilibrium may, at least in part, explain memory in quasispecies populations.

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Wilke, Claus O.0000-0002-7470-9261
Additional Information: © 2003 Wilke and Novella; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. The electronic version of this article is the complete one and can be found online at: Received 28 April 2003; Accepted 9 June 2003; Published 9 June 2003 COW was supported by the NSF under Contract No. DEB-9981397; ISN was supported by NIH grant AI45686.
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PubMed Central ID:PMC165440
Record Number:CaltechAUTHORS:WILbmcm03
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ID Code:1147
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Deposited On:23 Dec 2005
Last Modified:01 Jun 2023 23:37

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