Department of Cell Biology and Molecular Genetics, Maryland Pathogen Research Institute, 3134 Bioscience Research Building, University of Maryland, College Park, MD 20742, USA.
Department of Cell Biology and Molecular Genetics, Maryland Pathogen Research Institute, 3134 Bioscience Research Building, University of Maryland, College Park, MD 20742, USA.
J Mol Biol. 2022 Mar 30;434(6):167374. doi: 10.1016/j.jmb.2021.167374. Epub 2021 Dec 1.
An effective innate antiviral response is critical for the mitigation of severe disease and host survival following infection. In vivo, the innate antiviral response is triggered by cells that detect the invading pathogen and then communicate through autocrine and paracrine signaling to stimulate the expression of genes that inhibit viral replication, curtail cell proliferation, or modulate the immune response. In other words, the innate antiviral response is complex and dynamic. Notably, in the laboratory, culturing viruses and assaying viral life cycles frequently utilizes cells that are derived from tissues other than those that support viral replication during natural infection, while the study of viral pathogenesis often employs animal models. In recapitulating the human antiviral response, it is important to consider that variation in the expression and function of innate immune sensors and antiviral effectors exists across species, cell types, and cell differentiation states, as well as when cells are placed in different contexts. Thus, to gain novel insight into the dynamics of the host response and how specific sensors and effectors impact infection kinetics by a particular virus, the model system must be selected carefully. In this review, we briefly introduce key signaling pathways involved in the innate antiviral response and highlight how these differ between systems. We then review the application of tissue-engineered or 3D models for studying the antiviral response, and suggest how these in vitro culture systems could be further utilized to assay physiologically-relevant host responses and reveal novel insight into virus-host interactions.
有效的先天抗病毒反应对于减轻感染后严重疾病和宿主生存至关重要。在体内，先天抗病毒反应是由检测入侵病原体的细胞触发的，然后通过自分泌和旁分泌信号进行通讯，以刺激抑制病毒复制、限制细胞增殖或调节免疫反应的基因表达。换句话说，先天抗病毒反应是复杂和动态的。值得注意的是，在实验室中，培养病毒并检测病毒生命周期通常利用的是来自天然感染中不支持病毒复制的组织的细胞，而病毒发病机制的研究通常采用动物模型。在再现人类抗病毒反应时，必须考虑到先天免疫传感器和抗病毒效应物的表达和功能在不同物种、细胞类型和细胞分化状态以及细胞处于不同环境时存在差异。因此，为了深入了解宿主反应的动态以及特定传感器和效应物如何影响特定病毒的感染动力学，必须仔细选择模型系统。在这篇综述中，我们简要介绍了先天抗病毒反应中涉及的关键信号通路，并强调了这些通路在不同系统中的差异。然后，我们回顾了组织工程或 3D 模型在抗病毒反应研究中的应用，并提出了如何进一步利用这些体外培养系统来检测生理相关的宿主反应，并揭示病毒-宿主相互作用的新见解。
