Bretscher Michael T, Althaus Christian L, Müller Viktor, Bonhoeffer Sebastian
Ecology & Evolution, ETH Zürich, Switzerland.
Bioessays. 2004 Feb;26(2):180-8. doi: 10.1002/bies.10386.
The rapid evolution of drug resistance remains a major obstacle for HIV therapy. The capacity of the virus for recombination is widely believed to facilitate the evolution of drug resistance. Here, we challenge this intuitive view. We develop a population genetic model of HIV replication that incorporates the processes of mutation, cellular superinfection, and recombination. We show that cellular superinfection increases the abundance of low fitness viruses at the expense of the fittest strains due to the mixing of viral proteins during virion assembly. Moreover, we argue that whether recombination facilitates the evolution of drug resistance depends critically on how resistance mutations interact to determine viral fitness. Contrary to the commonly held belief, we find that, under the most plausible biological assumptions, recombination is expected to slow down the rate of evolution of multi-drug-resistant virus during therapy.
耐药性的快速演变仍然是艾滋病病毒治疗的一个主要障碍。人们普遍认为，病毒的重组能力促进了耐药性的演变。在此，我们对这一直观观点提出质疑。我们构建了一个艾滋病病毒复制的群体遗传模型，该模型纳入了突变、细胞双重感染和重组过程。我们发现，由于病毒粒子组装过程中病毒蛋白的混合，细胞双重感染会以最适应菌株为代价增加低适应性病毒的丰度。此外，我们认为重组是否促进耐药性的演变关键取决于耐药突变如何相互作用以决定病毒适应性。与普遍看法相反，我们发现，在最合理的生物学假设下，重组预计会减缓治疗期间多药耐药病毒的进化速度。
