Stochastic theory of early viral infection: continuous versus burst production of virions.
Stochastic theory of early viral infection: continuous versus burst production of virions.
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DOI：
10.1371/journal.pcbi.1001058
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发表时间：
2011-02-03
影响因子：
4.3
通讯作者：
Perelson AS
中科院分区：
文献类型：
--
作者：
Pearson JE;Krapivsky P;Perelson AS
从受感染细胞产生的病毒可以连续发生，也可以突然发生，通常会杀死细胞。对于艾滋病毒感染，两种生产模式都被提出。作为常微分方程组的标准病毒动力学模型不能区分这两种病毒产生模式，因为只要受感染的细胞在其寿命期间产生相同总数的病毒体，预测的动力学就相同。在这里，我们表明，在病毒感染的随机模型中，两种模式的病毒生产产生不同的早期动态。此外，我们分析确定了任何数量的病毒体和受感染细胞引发的感染达到灭绝的概率，即病毒体和受感染细胞的种群消失的状态，并表明这也有不同的解决方案用于连续和爆发生产。我们还计算了建立感染的时间分布以及从单个病毒体以及从单个感染细胞开始的两种病毒体生产模式的灭绝时间分布。艾滋病毒感染和治疗的动力学已经使用常微分方程模型进行了广泛的研究。最近关于艾滋病毒传播的研究表明，大多数性传播感染是由单一病毒或受感染的细胞开始的。这一观察结果，加上事实上，成功的艾滋病毒传播只发生在1/100至1/1000性交行为表明，感染的早期事件是随机的。在这里，我们开发了一个随机模型的HIV感染，并使用它来表征动态的早期感染时，病毒从细胞中释放连续或在一个突发。我们发现，这些机制的病毒生产产生不同的早期动态，不同的灭绝概率和不同的时间分布，以建立感染。在确定性模型中，这些病毒产生模式是不可区分的。
Viral production from infected cells can occur continuously or in a burst that generally kills the cell. For HIV infection, both modes of production have been suggested. Standard viral dynamic models formulated as sets of ordinary differential equations can not distinguish between these two modes of viral production, as the predicted dynamics is identical as long as infected cells produce the same total number of virions over their lifespan. Here we show that in stochastic models of viral infection the two modes of viral production yield different early term dynamics. Further, we analytically determine the probability that infections initiated with any number of virions and infected cells reach extinction, the state when both the population of virions and infected cells vanish, and show this too has different solutions for continuous and burst production. We also compute the distributions of times to establish infection as well as the distribution of times to extinction starting from both a single virion as well as from a single infected cell for both modes of virion production. The dynamics of HIV infection and treatment has been extensively studied using ordinary differential equation models. Recent work on HIV transmission has suggested that most sexually transmitted infections are started by a single virus or infected cell. This observation coupled with the fact that successful HIV transmission only occurs in 1 per 100 to 1 per 1000 coital acts suggests that early events in infection are stochastic. Here we develop a stochastic model of HIV infection and use it to characterize the dynamics of early infection when virus is released from cells either continuously or in a burst. We show that these mechanisms of viral production produce different early dynamics, with different probabilities of extinction and different distributions of time to establish infection. In deterministic models, these modes of viral production are indistinguishable.
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DOI：
10.1073/pnas.0707449104
发表时间：
2007-11-27
影响因子：
11.1
作者：
Chen, Hannah Yuan;Di Mascio, Michele;Zhang, Linqi
通讯作者：
Zhang, Linqi
DOI：
10.1084/jem.20082831
发表时间：
2009-05-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Keele BF;Li H;Learn GH;Hraber P;Giorgi EE;Grayson T;Sun C;Chen Y;Yeh WW;Letvin NL;Mascola JR;Nabel GJ;Haynes BF;Bhattacharya T;Perelson AS;Korber BT;Hahn BH;Shaw GM
通讯作者：
Shaw GM
DOI：
10.1073/pnas.0802203105
发表时间：
2008-05-27
影响因子：
11.1
作者：
Keele, Brandon F.;Giorgi, Elena E.;Shaw, George M.
通讯作者：
Shaw, George M.
影响因子：
3.7
作者：
Fischer W;Ganusov VV;Giorgi EE;Hraber PT;Keele BF;Leitner T;Han CS;Gleasner CD;Green L;Lo CC;Nag A;Wallstrom TC;Wang S;McMichael AJ;Haynes BF;Hahn BH;Perelson AS;Borrow P;Shaw GM;Bhattacharya T;Korber BT
通讯作者：
Korber BT
DOI：
10.1073/pnas.93.14.7247
发表时间：
1996-07-09
影响因子：
11.1
作者：
Herz, AVM;Bonhoeffer, S;Nowak, MA
通讯作者：
Nowak, MA