Current estimates for HIV-1 production imply rapid viral clearance in lymphoid tissues.
Current estimates for HIV-1 production imply rapid viral clearance in lymphoid tissues.
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DOI：
10.1371/journal.pcbi.1000906
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发表时间：
2010-09-02
影响因子：
4.3
通讯作者：
Perelson AS
中科院分区：
文献类型：
--
作者：
De Boer RJ;Ribeiro RM;Perelson AS
最近据估计，单个HIV-1感染细胞在其生命周期内产生的病毒颗粒在两种或更多种之间。由于游离病毒与生产性感染细胞之比的全身估计值小于或远小于，因此必须迅速清除单个病毒体。这似乎很难与大部分全身病毒被困在滤泡树突细胞上的事实相一致，在那里它可以存活数月。恒河猴和慢性感染患者血液中病毒清除率的巨大差异也很难调和。在这里，我们试图通过考虑不同器官中的病毒粒子清除率和它们之间的病毒粒子交换率来调和这些看似矛盾的观察结果。主要结果是，淋巴组织中游离病毒的人均清除率应该是快的，淋巴组织和血液之间的病毒体交换率应该是慢的，相对较慢的先前估计的病毒体从血液中清除率对应于病毒体从血液流出到病毒最终被清除的其他器官的速率。一个感染了艾滋病病毒HIV-1的人类细胞在其短暂的生命周期内可能会产生不止新的病毒颗粒。在慢性感染HIV-1的患者中，可以估计，平均而言，每个生产性感染细胞中的游离病毒颗粒要少得多。这表明单个病毒颗粒从体内清除的速度必须很快。然而，大多数病毒是长寿的，因为它被困在滤泡树突细胞上。我们试图调和这些看似矛盾的观察估计病毒粒子清除率在不同的器官，它们之间的病毒粒子交换率，使用数学建模方法。我们发现单个病毒颗粒从淋巴组织中迅速清除，而病毒在淋巴组织和血液之间交换的速度很慢。
It has recently been estimated that a single HIV-1 infected cell produces between and more than viral particles over its life span. Since body-wide estimates of the ratio of free virus to productively infected cells are smaller than and much smaller than , individual virions must be cleared rapidly. This seems difficult to reconcile with the fact that most of the total body virus is trapped on follicular dendritic cells where it can survive for many months. It has also been difficult to reconcile the vast difference in the rates at which the virus is cleared from the blood in rhesus macaques and in chronically infected patients. Here we attempt to reconcile these seemingly contradictory observations by considering the virion clearance rate in various organs and the virion exchange rates between them. The main results are that the per capita clearance rate of free virus in lymphoid tissue should be fast, the virion exchange rate between lymphoid tissue and the blood should be slow, and the comparatively slow previous estimates for the virion clearance rate from the blood correspond to the rate of virion efflux from the blood to other organs where the virus is ultimately cleared. A human cell that is infected with the AIDS virus HIV-1 may produce more than new viral particles over its short life span. In patients chronically infected with HIV-1, one can estimate that on average there are much less than free viral particles per productively infected cell. This suggests that the rate at which individual virus particles are cleared from the body must be fast. Most of the virus is long-lived, however, because it is trapped on follicular dendritic cells. We attempt to reconcile these seemingly contradictory observations by estimating the virion clearance rate in various organs, and the virion exchange rates between them, using a mathematical modeling approach. We find that individual virus particles are cleared rapidly from the lymphoid tissue, and that the rate at which virus is exchanged between lymphoid tissue and the blood is slow.
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DOI：
10.1073/pnas.190065897
发表时间：
2000-09-26
影响因子：
11.1
作者：
Hlavacek, WS;Stilianakis, NI;Perelson, AS
通讯作者：
Perelson, AS
DOI：
10.1073/pnas.0707449104
发表时间：
2007-11-27
影响因子：
11.1
作者：
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通讯作者：
Zhang, Linqi
影响因子：
2.6
作者：
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通讯作者：
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影响因子：
5.4
作者：
Zhang, LQ;Dailey, PJ;Ho, DD
通讯作者：
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影响因子：
30.3
作者：
He, Weijing;Neil, Stuart;Kulkarni, Hemant;Wright, Edward;Agan, Brian K.;Marconi, Vincent C.;Dolan, Matthew J.;Weiss, Robin A.;Ahujal, Sunil K.
通讯作者：
Ahujal, Sunil K.