Isabel S. Novella | Searcharxiv

arXiv2004

Replication at periodically changing multiplicity of infection promotes stable coexistence of competing viral populations

RNA viruses are a widely used tool to study evolution experimentally. Many standard protocols of virus propagation and competition are done at nominally low multiplicity of infection (m.o.i.), but lead during one passage to two or more rounds of infection, of which the later ones are at high m.o.i. Here, we develop a model of the competition between wild type (wt) and a mutant under a regime of alternating m.o.i. We assume that the mutant is deleterious when it infects cells on its own, but derives a selective advantage when rare and coinfecting with wt, because it can profit from superior protein products created by the wt. We find that, under these assumptions, replication at alternating low and high m.o.i. may lead to the stable coexistence of wt and mutant for a wide range of parameter settings. The predictions of our model are consistent with earlier observations of frequency-dependent selection in VSV and HIV-1. Our results suggest that frequency-dependent selection may be common in typical evolution experiments with viruses.

q-bio.PE↗

arXiv2003

Phenotypic mixing and hiding may contribute to memory in viral quasispecies

Background. In a number of recent experiments with food-and-mouth disease virus, a deleterious mutant, was found to avoid extinction and remain in the population for long periods of time. This observation was called quasispecies memory. 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 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.). The mutant's 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.

physics.bio-ph↗