Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable.
Relative rate and location of intra-host HIV evolution to evade cellular immunity are predictable.
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DOI：
10.1038/ncomms11660
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发表时间：
2016-05-23
影响因子：
16.6
通讯作者：
Chakraborty AK
中科院分区：
文献类型：
--
作者：
Barton JP;Goonetilleke N;Butler TC;Walker BD;McMichael AJ;Chakraborty AK
人类免疫缺陷病毒(HIV)在感染者体内进化，以躲避宿主免疫系统的破坏，从而阻止对感染的有效免疫控制。在这里，我们结合进化动力学和统计物理的方法来模拟体内HIV序列的进化，预测17名急性HIV感染者在T细胞介导的免疫压力下的相对逃逸率和逃逸突变的位置。预测的逃避免疫反应的时间与临床观察的时间吻合得很好，我们表明逃脱的突变路径取决于上位性相互作用所致的病毒序列背景。预测逃逸途径的能力以及特定免疫反应维持控制的持续时间，为合理设计免疫治疗策略打开了大门，从而可能实现对艾滋病毒感染的长期控制。我们的方法使得能够在概率框架内预测人类病原体的宿主内进化。艾滋病毒在感染者体内进化，以躲避免疫系统的破坏。在这里，巴顿等人。结合进化动力学和统计物理学来模拟这一过程，成功地预测了一组艾滋病毒感染者病毒序列中逃逸突变的相对比率和位置。
Human immunodeficiency virus (HIV) evolves within infected persons to escape being destroyed by the host immune system, thereby preventing effective immune control of infection. Here, we combine methods from evolutionary dynamics and statistical physics to simulate in vivo HIV sequence evolution, predicting the relative rate of escape and the location of escape mutations in response to T-cell-mediated immune pressure in a cohort of 17 persons with acute HIV infection. Predicted and clinically observed times to escape immune responses agree well, and we show that the mutational pathways to escape depend on the viral sequence background due to epistatic interactions. The ability to predict escape pathways and the duration over which control is maintained by specific immune responses open the door to rational design of immunotherapeutic strategies that might enable long-term control of HIV infection. Our approach enables intra-host evolution of a human pathogen to be predicted in a probabilistic framework. HIV evolves within infected persons to escape being destroyed by the immune system. Here, Barton et al. combine evolutionary dynamics and statistical physics to simulate this process, successfully predicting the relative rate and location of escape mutations in viral sequences for a cohort of HIV-infected persons.