Wodarz D, Lloyd A L, Jansen V A, Nowak M A
Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, U.K.
J Theor Biol. 1999 Jan 7;196(1):101-13. doi: 10.1006/jtbi.1998.0816.
We analyse mathematical models comparing the in vivo dynamics of macrophage- and T cell infection by HIV. Experiments suggest that HIV can only replicate in activated T cells whereas cell activation may not be required for successful replication in macrophages. These assumptions lead to fundamentally different conditions required to establish a persistent infection in the two cell types. While persistent replication in macrophages is achieved if the basic reproductive ratio of the virus, R0, exceeds unity, the establishment of T cell infection may depend on a complex balance between host and viral parameters as well as initial conditions. More specifically, the replication rate of HIV needs to lie above a threshold level and the immune responsiveness of the host below a certain threshold for persistent T cell infection to be possible. In addition, initial virus load has to be intermediate and the initial abundance of CTLs low. Mathematical models predict that macrophage infection may be essential for the successful establishment of HIV in the primary phase of the infection. Acting as a reservoir, they allow the virus to evolve towards increased replication kinetics as well as away from immune recognition, thus paving the way for the rise of exclusively T cell tropic strains using the CXCR4-coreceptor.
我们分析了比较HIV感染巨噬细胞和T细胞体内动力学的数学模型。实验表明，HIV只能在活化的T细胞中复制，而在巨噬细胞中成功复制可能不需要细胞活化。这些假设导致在两种细胞类型中建立持续感染所需的根本不同条件。如果病毒的基本繁殖率R0超过1，则可在巨噬细胞中实现持续复制，而T细胞感染的建立可能取决于宿主和病毒参数以及初始条件之间的复杂平衡。更具体地说，HIV的复制率需要高于阈值水平，宿主的免疫反应性低于一定阈值，才有可能发生持续的T细胞感染。此外，初始病毒载量必须处于中等水平，初始CTL丰度较低。数学模型预测，巨噬细胞感染对于HIV在感染初期的成功建立可能至关重要。作为一个储存库，它们使病毒能够朝着增加复制动力学以及逃避免疫识别的方向进化，从而为使用CXCR4共受体的纯T细胞嗜性毒株的出现铺平道路。
