Estimating relative fitness in viral competition experiments

The relative fitness of viral variants has previously been defined as the s lope of the logarithmic ratio of the genotype or phenotype frequencies in t ime plots of pairwise competition experiments. Developing mathematical mode ls for such experiments by employing the conventional coefficient of select ions, we demonstrate that this logarithmic ratio gives the fitness differen ce, rather than the relative fitness. This fitness difference remains propo rtional to the actual replication rate realized in the particular experimen tal setup and hence cannot be extrapolated to other situations. Conversely, the conventional relative fitness (1 + s) should be more generic. We devel op an approach to compute the generic relative fitness in conventional comp etition experiments. This involves an estimation of the total viral replica tion during the experiment and requires an estimate of the average lifetime of productively infected cells. The novel approach is illustrated by estim ating the relative fitness, i.e., the relative replication rate, of a set o f zidovudine-resistant human immunodeficiency virus type I variants. A tool for calculating the relative fitness from observed changes in viral load a nd genotype (or phenotype) frequencies is publically available on the websi te at http://www-binf.bio.uu.nl/(similar to)rdb/fitness.html.