Duration of SHIV production by infected cells is not exponentially distributed: Implications for estimates of infection parameters and antiviral efficacy.
Duration of SHIV production by infected cells is not exponentially distributed: Implications for estimates of infection parameters and antiviral efficacy.
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DOI：
10.1038/srep42765
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发表时间：
2017-02-16
影响因子：
4.6
通讯作者：
Iwami S
中科院分区：
文献类型：
--
作者：
Beauchemin CA;Miura T;Iwami S
蚀相阶段的持续时间，从细胞感染到第一个病毒体后代的产生和释放，紧接着是病毒产生阶段，从第一个病毒体后代到最后一个病毒体后代，是病毒感染的重要步骤，通过设定感染进展的速度并调节对抗病毒治疗的反应。使用数学模型 (MM) 和体外 SHIV 感染 HSC-F 细胞的数据，我们再次证实了我们之前的发现，即日食阶段持续时间遵循胖尾分布，持续 19 小时（18-20 小时）。最重要的是，我们首次表明，持续 11 小时（9.8-12 小时）的病毒产生阶段持续时间遵循正态分布，而不是通常假设的指数分布。我们探讨了这一发现的意义及其对接受抗病毒治疗的艾滋病毒患者血浆病毒载量衰减分析的影响。我们发现，对日食和病毒产生阶段分布的错误假设可能会导致抗病毒功效的高估。此外，我们对整合酶抑制剂治疗下血浆 HIV 衰减率的预测提供了一个机会，以确认体内 HIV 产生持续时间是否也遵循正态分布，正如此处针对 SHIV 体外感染所证明的那样。
The duration of the eclipse phase, from cell infection to the production and release of the first virion progeny, immediately followed by the virus-production phase, from the first to the last virion progeny, are important steps in a viral infection, by setting the pace of infection progression and modulating the response to antiviral therapy. Using a mathematical model (MM) and data for the infection of HSC-F cells with SHIV in vitro, we reconfirm our earlier finding that the eclipse phase duration follows a fat-tailed distribution, lasting 19 h (18–20 h). Most importantly, for the first time, we show that the virus-producing phase duration, which lasts 11 h (9.8–12 h), follows a normal-like distribution, and not an exponential distribution as is typically assumed. We explore the significance of this finding and its impact on analysis of plasma viral load decays in HIV patients under antiviral therapy. We find that incorrect assumptions about the eclipse and virus-producing phase distributions can lead to an overestimation of antiviral efficacy. Additionally, our predictions for the rate of plasma HIV decay under integrase inhibitor therapy offer an opportunity to confirm whether HIV production duration in vivo also follows a normal distribution, as demonstrated here for SHIV infections in vitro.