Recombination in HIV and the evolution of drug resistance:: for better or for worse?
Recombination in HIV and the evolution of drug resistance:: for better or for worse?
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DOI：
10.1002/bies.10386
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发表时间：
2004-02-01
期刊：
影响因子：
4
通讯作者：
Bonhoeffer, S
中科院分区：
文献类型：
--
作者：
Bretscher, MT;Althaus, CL;Bonhoeffer, S
耐药性的快速演变仍然是艾滋病毒治疗的主要障碍。人们普遍认为病毒的重组能力促进了耐药性的进化。在这里，我们挑战这种直观的观点。我们开发了HIV复制的群体遗传模型，该模型结合了突变、细胞重复感染和重组的过程。我们发现，由于病毒粒子组装过程中病毒蛋白的混合，细胞重叠感染以牺牲最适合的菌株为代价，增加了低适合度病毒的丰度。此外，我们认为重组是否促进耐药性的进化主要取决于耐药性突变如何相互作用以确定病毒适应性。与普遍持有的信念相反，我们发现，在最合理的生物学假设下，重组有望减缓治疗期间多重耐药病毒的进化速度。(C) 2004 Wiley期刊有限公司
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. (C) 2004 Wiley Periodicals, Inc.