Principles Governing Establishment versus Collapse of HIV-1 Cellular Spread
Principles Governing Establishment versus Collapse of HIV-1 Cellular Spread
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DOI：
10.1016/j.chom.2019.10.006
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发表时间：
2019-12-11
影响因子：
30.3
通讯作者：
Koup, Richard A.
中科院分区：
文献类型：
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作者：
Hataye, Jason M.;Casazza, Joseph P.;Koup, Richard A.
人口普查较低的人口可能会灭绝，或者转而呈指数增长并牢固确立。对于宿主内的病原体来说，这一关键事件是否发生可能是健康与疾病之间的区别。在这里，我们通过将随机模型与实验室实验相结合，定义了控制 HIV-1 在细胞间传播是否失败或建立的原则。在未从头感染的情况下体外激活潜伏感染的 CD4 T 细胞后，随机细胞分裂和死亡导致初始病毒释放量的高度可变性。由于释放的具有复制能力的病毒数量不足，向指数级 HIV-1 传播的转变常常会失败。当多个受感染细胞产生的病毒超过临界群体规模时，就会出现指数增长。我们定量地定义了指数病毒传播的关键转变。阻止这一过程将阻止艾滋病毒传播或从潜伏病毒库中反弹。
A population at low census might go extinct or instead transition into exponential growth to become firmly established. Whether this pivotal event occurs for a within-host pathogen can be the difference between health and illness. Here, we define the principles governing whether HIV-1 spread among cells fails or becomes established by coupling stochastic modeling with laboratory experiments. Following ex vivo activation of latently infected CD4 T cells without de novo infection, stochastic cell division and death contributes to high variability in the magnitude of initial virus release. Transition to exponential HIV-1 spread often fails due to release of an insufficient amount of replication-competent virus. Establishment of exponential growth occurs when virus produced from multiple infected cells exceeds a critical population size. We quantitatively define the crucial transition to exponential viral spread. Thwarting this process would prevent HIV transmission or rebound from the latent reservoir.