Density-dependent selection in vesicular stomatitis virus

Abstract

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.

FIG. 1.

Relative fitness of MARM N as a function of the MOI. The solid line indicates the prediction from our model, the final equation in the Appendix, with s = 0.552.

FIG. 2.

Relative fitness of MARM N as a function of the initial frequency for an MOI of 1 (diamonds) and an MOI of 10 (circles). The solid lines indicate the predictions from our model, the final equation in the Appendix, with s = 0.552.

FIG. 3.

Decay of MARM N concentration in standard 24-h passages. The line represents an exponential fit to the data, exp(−0.36 − 0.59t), where t indicates the passage number.