Department of Infectious Diseases, Integrative Virology, University Hospital Heidelberg, 69120 Heidelberg, Germany.
BioQuant-Center for Quantitative Biology, Heidelberg University, 69120 Heidelberg, Germany.
Cells. 2020 Apr 30;9(5):1112. doi: 10.3390/cells9051112.
HIV-1 can use cell-free and cell-associated transmission modes to infect new target cells, but how the virus spreads in the infected host remains to be determined. We recently established 3D collagen cultures to study HIV-1 spread in tissue-like environments and applied iterative cycles of experimentation and computation to develop a first in silico model to describe the dynamics of HIV-1 spread in complex tissue. These analyses (i) revealed that 3D collagen environments restrict cell-free HIV-1 infection but promote cell-associated virus transmission and (ii) defined that cell densities in tissue dictate the efficacy of these transmission modes for virus spread. In this review, we discuss, in the context of the current literature, the implications of this study for our understanding of HIV-1 spread in vivo, which aspects of in vivo physiology this integrated experimental-computational analysis takes into account, and how it can be further improved experimentally and in silico.
HIV-1 可以通过游离病毒和细胞相关的传播模式感染新的靶细胞，但病毒在感染宿主中的传播方式仍有待确定。我们最近建立了 3D 胶原培养物来研究 HIV-1 在组织样环境中的传播，并应用反复的实验和计算循环来开发第一个计算机模型来描述 HIV-1 在复杂组织中的传播动力学。这些分析结果表明：(i)3D 胶原环境限制游离 HIV-1 的感染，但促进细胞相关病毒的传播；(ii)组织中的细胞密度决定了这些传播模式对病毒传播的有效性。在这篇综述中，我们结合当前的文献，讨论了这项研究对我们理解 HIV-1 在体内传播的意义，以及综合实验-计算分析考虑了体内生理学的哪些方面，以及如何进一步在实验和计算上进行改进。
