Theoretical Biology and Biophysics Group, MS K710, Los Alamos National Laboratory, Los Alamos, NM 87545, USA.
J Virol. 2010 May;84(9):4302-10. doi: 10.1128/JVI.02284-09. Epub 2010 Feb 10.
A recent experiment involving simian immunodeficiency virus (SIV) infection of macaques revealed that the infectivity of this virus decreased over the first few months of infection. Based on this observation, we introduce a viral dynamic model in which viral infectivity varies over time. The model is fit to viral load data from eight (donor) monkeys infected by intravaginal inoculation of SIVmac251, three monkeys infected by intravenous inoculation of virus isolated from the donors during the ramp-up phase of acute infection, and three monkeys infected by intravenous inoculation of virus isolated at the viral set-point. Although we only analyze data from 14 monkeys, the new model with time-dependent infectivity seems to fit the data significantly better than a widely used model with constant infectivity (P = 2.44 x 10(-11)). Our results indicate that plasma virus infectivity on average decays approximately 8-fold (95% confidence interval [CI] = 5.1 to 10.3) over the course of acute infection, with the decay occurring exponentially with an average rate of 0.28 day(-1) (95% CI = 0.14 to 0.42 day(-1)). The decay rate in set point plasma virus recipient animals is approximately 16 times slower than in ramp-up plasma virus recipient animals and approximately 6 times slower than in donor animals. Throughout acute infection up to the set-point, the infection rate is higher in ramp-up plasma virus recipient animals than in set-point plasma virus recipient animals. These results show that the infectivity depends upon the source of viral infection.
最近一项涉及恒河猴免疫缺陷病毒(SIV)感染的实验表明,该病毒的感染性在感染的最初几个月内会下降。基于这一观察结果,我们引入了一个病毒动力学模型,其中病毒的感染力随时间变化。该模型适用于通过阴道内接种 SIVmac251 感染的 8 只(供体)猴子的病毒载量数据、3 只通过静脉内接种感染急性感染上升阶段从供体中分离出的病毒的猴子的病毒载量数据,以及 3 只通过静脉内接种感染在病毒设定点时分离出的病毒的猴子的病毒载量数据。尽管我们只分析了 14 只猴子的数据,但具有时间依赖性感染力的新模型似乎比具有恒定感染力的广泛使用的模型更能显著拟合数据(P = 2.44 x 10(-11))。我们的结果表明,在急性感染过程中,血浆病毒感染力平均下降约 8 倍(95%置信区间 [CI] = 5.1 至 10.3),下降呈指数衰减,平均衰减率为 0.28 天(95% CI = 0.14 至 0.42 天)。在设定点血浆病毒受者动物中,衰减率比在上升期血浆病毒受者动物中慢约 16 倍,比在供体动物中慢约 6 倍。在整个急性感染直至设定点期间,上升期血浆病毒受者动物的感染率高于设定点血浆病毒受者动物。这些结果表明,感染性取决于病毒感染的来源。