Department of Mathematics, The University of Texas at Austin, Austin, TX 78712, USA.
J Theor Biol. 2009 Nov 7;261(1):67-73. doi: 10.1016/j.jtbi.2009.07.014. Epub 2009 Jul 21.
We analyze how lethal mutagenesis operates in a compartmentalized host. We assume that different compartments receive different amounts of mutagen and that virions can migrate among compartments. We address two main questions: (1) To what extent can refugia, i.e., compartments that receive little mutagen, prevent extinction? (2) Does migration among compartments limit the effectiveness of refugia? We find that if there is little migration, extinction has to be achieved separately in all compartments. In this case, the total dose of mutagen administered to the host needs to be so high that the mutagen is effective even in the refugia. By contrast, if migration is extensive, then lethal mutagenesis is effective as long as the average growth in all compartments is reduced to below replacement levels. The effectiveness of migration is governed by the ratio of virion replication and death rates, R(0). The smaller R(0), the less migration is necessary to neutralize refugia and the less mutagen is necessary to achieve extinction at high migration rates.
我们分析了在分隔宿主中致死性诱变是如何作用的。我们假设不同的隔间接收到不同数量的诱变剂，并且病毒粒子可以在隔间之间迁移。我们主要关注两个问题：（1）避难所（即接收到少量诱变剂的隔间）在多大程度上可以防止灭绝？（2）隔间之间的迁移是否会限制避难所的有效性？我们发现，如果迁移很少，则必须在所有隔间中分别达到灭绝。在这种情况下，需要给宿主施用如此高剂量的诱变剂，以至于即使在避难所中，诱变剂也是有效的。相比之下，如果迁移广泛，那么只要所有隔间中的平均增长率降低到替代水平以下，致死性诱变就是有效的。迁移的有效性由病毒粒子复制和死亡率的比率 R(0) 来决定。R(0)越小，为了中和避难所和为了在高迁移率下实现灭绝而需要的迁移就越少。
