Marée A F, Keulen W, Boucher C A, De Boer R J
Theoretical Biology, Utrecht University, Utrecht, The Netherlands.
J Virol. 2000 Dec;74(23):11067-72. doi: 10.1128/jvi.74.23.11067-11072.2000.
The relative fitness of viral variants has previously been defined as the slope of the logarithmic ratio of the genotype or phenotype frequencies in time plots of pairwise competition experiments. Developing mathematical models for such experiments by employing the conventional coefficient of selection s, we demonstrate that this logarithmic ratio gives the fitness difference, rather than the relative fitness. This fitness difference remains proportional to the actual replication rate realized in the particular experimental setup and hence cannot be extrapolated to other situations. Conversely, the conventional relative fitness (1 + s) should be more generic. We develop an approach to compute the generic relative fitness in conventional competition experiments. This involves an estimation of the total viral replication during the experiment and requires an estimate of the average lifetime of productively infected cells. The novel approach is illustrated by estimating the relative fitness, i.e., the relative replication rate, of a set of zidovudine-resistant human immunodeficiency virus type 1 variants. A tool for calculating the relative fitness from observed changes in viral load and genotype (or phenotype) frequencies is publically available on the website at http://www-binf.bio.uu.nl/( approximately )rdb/fitness.html.
病毒变体的相对适应性先前被定义为成对竞争实验时间图中基因型或表型频率对数比的斜率。通过使用传统的选择系数s为此类实验建立数学模型，我们证明这种对数比给出的是适应性差异，而非相对适应性。这种适应性差异仍然与在特定实验设置中实现的实际复制率成比例，因此不能外推到其他情况。相反，传统的相对适应性（1 + s）应该更具通用性。我们开发了一种在传统竞争实验中计算通用相对适应性的方法。这涉及估计实验期间的病毒总复制量，并且需要估计有效感染细胞的平均寿命。通过估计一组齐多夫定耐药的1型人类免疫缺陷病毒变体的相对适应性，即相对复制率，来说明这种新方法。可在网站http://www-binf.bio.uu.nl/( approximately )rdb/fitness.html上公开获取一个根据观察到的病毒载量和基因型（或表型）频率变化来计算相对适应性的工具。
