Modeling Innate Antiviral Immunity in Physiological Context.
Modeling Innate Antiviral Immunity in Physiological Context.
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在生理学背景下建立天然抗病毒免疫模型。
DOI：
10.1016/j.jmb.2021.167374
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发表时间：
2022-03-30
影响因子：
5.6
通讯作者：
Scull MA
中科院分区：
文献类型：
--
作者：
Goldstein ME;Scull MA
有效的先天抗病毒反应对于减轻严重疾病和感染后宿主存活至关重要。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传导刺激抑制病毒复制、抑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，培养病毒和分析病毒生命周期经常使用来自组织的细胞，而不是那些在自然感染期间支持病毒复制的细胞，而病毒发病机制的研究通常使用动物模型。在概述人类抗病毒反应时，重要的是要考虑到先天免疫传感器和抗病毒效应器的表达和功能的变化存在于物种、细胞类型和细胞分化状态中，以及当细胞处于不同的环境中时。因此，为了获得对宿主反应动力学以及特定传感器和效应器如何影响特定病毒感染动力学的新见解，必须仔细选择模型系统。在这篇综述中，我们简要介绍了涉及先天抗病毒反应的关键信号通路，并强调了这些系统之间的差异。然后，我们回顾了组织工程或3D模型在研究抗病毒反应方面的应用，并建议如何进一步利用这些体外培养系统来分析生理相关的宿主反应，并揭示病毒与宿主相互作用的新见解。
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.
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DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
--
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Casanova JL
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
4.6
作者：
Brooks, AR;Lelkes, PI;Rubanyi, GM
通讯作者：
Rubanyi, GM
影响因子：
30.5
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通讯作者：
--
DOI：
10.1084/jem.20210583
发表时间：
2021-08-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cheemarla NR;Watkins TA;Mihaylova VT;Wang B;Zhao D;Wang G;Landry ML;Foxman EF
通讯作者：
Foxman EF