Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques

Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques
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DOI:
10.1073/pnas.0707449104
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发表时间:
2007-11-27
影响因子:
11.1
通讯作者:
Zhang, Linqi
Zhang, Linqi
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Chen, Hannah Yuan;Di Mascio, Michele;Zhang, Linqi

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构建了一种仅经历一轮感染和复制的单周期猿猴免疫缺陷病毒(scSIV),以计算siv感染细胞在体内产生的病毒总数。4只Mamu-A*01恒河猴通过体外感染和自身细胞静脉回输两种方法接种scSIV,接种间隔11周。每次接种后,血浆病毒载量在1 ~ 2.5天内达到峰值,然后在2周内呈一到两期指数下降至检测限以下。虽然在第二次接种后,观察到每只动物siv特异性细胞毒性T淋巴细胞水平较高,抗体反应适度增加,但感染细胞的衰变率仅受到最小影响。用数学模型分析病毒载量数据,第一次接种和第二次接种的体内病毒爆发大小分别为每细胞4.0 × 10(4)和5.5 × 10(4)个病毒粒子,两次接种之间无显著差异。这一估计,结合我们之前对SIV和HIV感染期间其他定量病毒和细胞参数的理解,为病毒产生的动态过程及其与受感染宿主的相互作用提供了重要的见解。
A single-cycle simian immunodeficiency virus (scSIV) that undergoes only one round of infection and replication was constructed to calculate the total number of virons produced by an SIV-infected cell in vivo. Four Mamu-A*01 rhesus macaques were inoculated on two occasions 11 weeks apart with the scSIV by ex vivo infection and i.v. reinfusion of autologous cells. After each inoculation, plasma viral loads peaked between 1 and 2.5 days and then declined exponentially in one or two phases to below detection limits within 2 weeks. Although higher levels of SIV-specific cytotoxic T lymphocytes and modest increases in antibody responses were observed for each animal after the second inoculation, decay rates of the infected cells were only minimally affected. Analyzing the viral load data with a mathematical model, the in vivo viral burst size averaged 4.0 x 10(4) and 5.5 x 10(4) virions per cell for the first and second inoculations, respectively, with no significant difference between the two inoculations. This estimate, in conjunction with our prior understanding of other quantitative viral and cellular parameters during SIV and HIV infection, provides critical insights into the dynamic process of viral production and its interplay with the infected host in vivo.