Pyroptosis, superinfection, and the maintenance of the latent reservoir in HIV-1 infection.
Pyroptosis, superinfection, and the maintenance of the latent reservoir in HIV-1 infection.
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DOI：
10.1038/s41598-017-04130-9
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发表时间：
2017-06-19
影响因子：
4.6
通讯作者：
Levy DN
中科院分区：
文献类型：
--
作者：
Wodarz D;Levy DN
潜伏感染T细胞的长期储存库阻止抗逆转录病毒治疗消除HIV-1感染。因此，进一步了解潜伏期产生和维持的动态对改善治疗结果至关重要。使用数学模型和实验，我们认为，死亡的潜伏感染细胞引起的pyroptosis，或在较小程度上由重叠感染，可能是关键的机制，以占的大小和组成的潜伏水库。细胞死亡是一种细胞死亡形式，当有效感染的细胞试图进行病毒的细胞间传播时，会发生在静息（因此是潜伏感染）的T细胞中。通过生产性病毒对潜伏感染细胞的重复感染可以类似地通过活跃的病毒复制和导致的细胞病变去除那些细胞。提出的数学模型可以解释一些以前发表的临床观察，包括潜伏水库的大小和急性HIV感染的病毒载量的关系，在慢性感染的潜伏水库的测量，和野生型病毒的替代CTL逃逸突变体内的潜伏水库。基本的病毒动力学潜伏期模型没有考虑到细胞自燃、重复感染或其他潜在的复杂性，因此无法解释这些数据。
A long-lived reservoir of latently infected T cells prevents antiretroviral therapy from eliminating HIV-1 infection. Furthering our understanding of the dynamics of latency generation and maintenance is therefore vital to improve treatment outcome. Using mathematical models and experiments, we suggest that the death of latently infected cells brought about by pyroptosis, or to a lesser extent by superinfection, might be key mechanisms to account for the size and composition of the latent reservoir. Pyroptosis is a form of cell death that occurs in a resting (and thus latently infected) T cell when a productively infected cell attempts cell-to-cell transmission of virus. Superinfection of latently infected cells by productive virus could similarly remove those cells through active virus replication and resulting cytopathicity. The mathematical models presented can explain a number of previously published clinical observations including latent reservoir size and the relationships to viral load in acute HIV infection, measurements of the latent reservoir in chronic infection, and the replacement of wild-type virus by CTL escape mutants within the latent reservoir. Basic virus dynamics models of latency that do not take into account pyroptosis, superinfection, or other potential complexities cannot account for the data.