Daniel D Reissig | PubMed Health

PubMed2004

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

RNA viruses are widely used 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 vesicular stomatitis virus and human immunodeficiency virus type 1. Our results suggest that frequency-dependent selection may be common in typical evolution experiments with viruses.

Cell Line↗

PubMed2004

Density-dependent selection in vesicular stomatitis virus.

We used vesicular stomatitis virus to test the effect of complementation on the relative fitness of a deleterious mutant, monoclonal antibody-resistant mutant (MARM) N, in competition with its wild-type ancestor. We carried out competitions of MARM N and wild-type populations at different multiplicities of infection (MOIs) and initial ratios of the wild type to the mutant and found that the fitness of MARM N relative to that of the wild type is very sensitive to changes in the MOI (i.e., the degree of complementation) but depends little, if at all, on the initial frequencies of MARM N and the wild type. Further, we developed a mathematical model under the assumption that during coinfection both viruses contribute to a common pool of protein products in the infected cell and that they both exploit this common pool equally. Under such conditions, the fitness of all virions that coinfect a cell is the average fitness in the absence of coinfection of that group of virions. In the absence of coinfection, complementation cannot take place and the relative fitness of each competitor is only determined by the selective value of its own products. We found good agreement between our experimental results and the model predictions, which suggests that the wild type and MARM N freely share all of their gene products under coinfection.

Animals↗