RIG-I特定细胞在抗病毒反应中的作用
转载请注明来自丁香园
Field: Immunology
Article Title: Cell type-specific involvement of RIG-I in antiviral response
Authors: Kato, H;Sato, S;Yoneyama, M;Yamamoto, M;Uematsu, S;Matsui, K;Tsujimura, T;Takeda, K;Fujita, T;Takeuchi, O;Akira, S
Journal: IMMUNITY
Volume: 23
Issue: 1
Page: 19-28
Q： Why do you think your paper is highly cited?
A：The recognition of RNA virus by the host and the subsequent antiviral responses has been studied for many years. Initial recognition of viral components such as double-stranded RNA (dsRNA) led to the rapid induction of type I interferons and proinflammatory cytokines.
Recently, toll-like receptors (TLRs) and retinoic acid-inducible gene-I (RIG-I) have been implicated in the detection of viral dsRNA and the induction of type I interferons. However, it was not clear how these viral detectors contributed in vivo in host defense against viruses.
This paper describes how RIG-I is essential for the initial recognition of various RNA viruses in many cell-types except that of plasmacytoid dendritic cells (pDCs). On the other hand, we found that pDCs, which are known to produce high amounts of interferon-α upon viral infection, utilize the TLR system, but not RIG-I. This is the first paper showing the function of RIG-I in vivo, in comparison with that of the TLR system.
Q： Does it describe a new discovery, methodology, or synthesis of knowledge?
A：This paper describes mice deficient in RIG-I and showed that RIG-I is critical for the induction of type I interferons and interferon-inducible genes in response to several RNA viruses, in most cell types except pDCs. The mice will be a valuable tool for studying the mechanisms of anti-viral host defense in vivo.
Q： Could you summarize the significance of your paper in layman's terms?
A：Production of type I interferons is vital for the initial host defense against viral infection. Mechanisms for the recognition of viruses have been investigated by various researchers. This paper shows that RIG-I and the TLR system play a critical role in different cell types in the recognition of RNA viruses in vivo.
Modulation of machineries for interferon production will possibly lead to the development of efficient vaccines and the prevention of viral infection. In this aspect, an understanding of the precise mechanism for viral recognition is critical in designing appropriate strategies for clinical applications.
Q： How did you become involved in this research, and were any problems encountered along the way?
A：We have been interested in how the innate immune system recognizes pathogen-specific components, and we have been involved in the research of Toll-like receptors. We previously reported that TLR7 and TLR9 are the ligands for viral single-stranded RNA and DNA, respectively.
TLR3 has also been shown to recognize viral dsRNA. Nevertheless, we found that the TLR system is not necessarily essential to antiviral responses in vivo as shown in this paper. Therefore, we further explored novel machineries for the detection of viruses and the production of type I interferons.
Hiroki Kato, Ph.D. Student
Department of Host Defense
Research Institute for Microbial Diseases
Osaka University
Osamu Takeuchi, M.D., Ph.D.
Department of Host Defense
Research Institute for Microbial Diseases
Osaka University
Shizuo Akira, M.D., Ph.D.
Professor
Department of Host Defense
Research Institute for Microbial Diseases
Osaka University
问：为什么你认为你的论文有很高引用率？
答：病毒学家们对宿主如何识别RNA病毒以及如何激发抗病毒反应等问题进行了多年研究。识别病毒组分如双链RNA（dsRNA）能迅速诱导释放Ⅰ型干扰素和前炎性细胞因子。最新研究表明，Toll样受体（TLRs）和维甲酸诱导的Ⅰ型基因（RIG-Ⅰ）参与了病毒dsRNA的识别和Ⅰ型的诱导。然而，目前还不清楚病毒识别在体内如何引起宿主抗病毒反应。在该论文中，我们描绘了RIG-Ⅰ在除pDC外的多种细胞类型对不同RNA病毒识别过程中的重要作用。与此相对，被病毒感染后能产生大量α干扰素的pDCs利用TLR系统而不是RIG-Ⅰ识别RNA病毒的感染。该论文首次展示了RIG-Ⅰ在体内具有TLR系统类似的功能。
问：这篇论文是否描述了一种新发现、新方法或知识的综合？
答：该论文描述了RIG-Ⅰ缺陷小鼠，并展示了RIG-Ⅰ在除pDCs外的大量细胞类型抗一些RNA病毒反应中，Ⅰ型干扰素和干扰素诱导的基因表达中的重要作用。这种RIG-Ⅰ缺陷小鼠成为体内研究宿主抗病毒防御反应机制有价值的工具。
问：你能不能用通俗的语言总结一下您这篇论文的意义？
答：宿主抗病毒反应主要由Ⅰ型干扰素产生而激发。很多研究者对病毒识别机制进行了深入研究。我们的研究展示了RIG-Ⅰ和TLR系统在不同类型细胞对RNA病毒识别中的重要作用。产生干扰素的调控可能导致有效疫苗的发展以预防病毒感染。从这个角度看，制定合理的临床治疗策略取决于对病毒识别机制的深刻把握。
问：您是怎样开始介入这项研究的，在研究过程中遇到了哪些问题？
答：一直以来，我们对固有免疫系统如何识别病原体特异性组分的问题非常感兴趣，并且正在进行Toll样受体研究。我们曾报道了TLR7和TLR9分别是病毒单链RNA和DNA的受体。
TLR3被证实也能够识别病毒双链RNA。然而，正如论文中所揭示，发现TLR系统在体内抗病毒反应中并非必须。因此，我们对宿主在病毒识别和Ⅰ型干扰素的产生机制方面进行了研究。
编者按：本采访记录由丁香园网友迷北方的狼翻译。
编辑：西门吹血
Article Title: Cell type-specific involvement of RIG-I in antiviral response
Authors: Kato, H;Sato, S;Yoneyama, M;Yamamoto, M;Uematsu, S;Matsui, K;Tsujimura, T;Takeda, K;Fujita, T;Takeuchi, O;Akira, S
Journal: IMMUNITY
Volume: 23
Issue: 1
Page: 19-28
Q： Why do you think your paper is highly cited?
A：The recognition of RNA virus by the host and the subsequent antiviral responses has been studied for many years. Initial recognition of viral components such as double-stranded RNA (dsRNA) led to the rapid induction of type I interferons and proinflammatory cytokines.
Recently, toll-like receptors (TLRs) and retinoic acid-inducible gene-I (RIG-I) have been implicated in the detection of viral dsRNA and the induction of type I interferons. However, it was not clear how these viral detectors contributed in vivo in host defense against viruses.
This paper describes how RIG-I is essential for the initial recognition of various RNA viruses in many cell-types except that of plasmacytoid dendritic cells (pDCs). On the other hand, we found that pDCs, which are known to produce high amounts of interferon-α upon viral infection, utilize the TLR system, but not RIG-I. This is the first paper showing the function of RIG-I in vivo, in comparison with that of the TLR system.
Q： Does it describe a new discovery, methodology, or synthesis of knowledge?
A：This paper describes mice deficient in RIG-I and showed that RIG-I is critical for the induction of type I interferons and interferon-inducible genes in response to several RNA viruses, in most cell types except pDCs. The mice will be a valuable tool for studying the mechanisms of anti-viral host defense in vivo.
Q： Could you summarize the significance of your paper in layman's terms?
A：Production of type I interferons is vital for the initial host defense against viral infection. Mechanisms for the recognition of viruses have been investigated by various researchers. This paper shows that RIG-I and the TLR system play a critical role in different cell types in the recognition of RNA viruses in vivo.
Modulation of machineries for interferon production will possibly lead to the development of efficient vaccines and the prevention of viral infection. In this aspect, an understanding of the precise mechanism for viral recognition is critical in designing appropriate strategies for clinical applications.
Q： How did you become involved in this research, and were any problems encountered along the way?
A：We have been interested in how the innate immune system recognizes pathogen-specific components, and we have been involved in the research of Toll-like receptors. We previously reported that TLR7 and TLR9 are the ligands for viral single-stranded RNA and DNA, respectively.
TLR3 has also been shown to recognize viral dsRNA. Nevertheless, we found that the TLR system is not necessarily essential to antiviral responses in vivo as shown in this paper. Therefore, we further explored novel machineries for the detection of viruses and the production of type I interferons.
Hiroki Kato, Ph.D. Student
Department of Host Defense
Research Institute for Microbial Diseases
Osaka University
Osamu Takeuchi, M.D., Ph.D.
Department of Host Defense
Research Institute for Microbial Diseases
Osaka University
Shizuo Akira, M.D., Ph.D.
Professor
Department of Host Defense
Research Institute for Microbial Diseases
Osaka University
问：为什么你认为你的论文有很高引用率？
答：病毒学家们对宿主如何识别RNA病毒以及如何激发抗病毒反应等问题进行了多年研究。识别病毒组分如双链RNA（dsRNA）能迅速诱导释放Ⅰ型干扰素和前炎性细胞因子。最新研究表明，Toll样受体（TLRs）和维甲酸诱导的Ⅰ型基因（RIG-Ⅰ）参与了病毒dsRNA的识别和Ⅰ型的诱导。然而，目前还不清楚病毒识别在体内如何引起宿主抗病毒反应。在该论文中，我们描绘了RIG-Ⅰ在除pDC外的多种细胞类型对不同RNA病毒识别过程中的重要作用。与此相对，被病毒感染后能产生大量α干扰素的pDCs利用TLR系统而不是RIG-Ⅰ识别RNA病毒的感染。该论文首次展示了RIG-Ⅰ在体内具有TLR系统类似的功能。
问：这篇论文是否描述了一种新发现、新方法或知识的综合？
答：该论文描述了RIG-Ⅰ缺陷小鼠，并展示了RIG-Ⅰ在除pDCs外的大量细胞类型抗一些RNA病毒反应中，Ⅰ型干扰素和干扰素诱导的基因表达中的重要作用。这种RIG-Ⅰ缺陷小鼠成为体内研究宿主抗病毒防御反应机制有价值的工具。
问：你能不能用通俗的语言总结一下您这篇论文的意义？
答：宿主抗病毒反应主要由Ⅰ型干扰素产生而激发。很多研究者对病毒识别机制进行了深入研究。我们的研究展示了RIG-Ⅰ和TLR系统在不同类型细胞对RNA病毒识别中的重要作用。产生干扰素的调控可能导致有效疫苗的发展以预防病毒感染。从这个角度看，制定合理的临床治疗策略取决于对病毒识别机制的深刻把握。
问：您是怎样开始介入这项研究的，在研究过程中遇到了哪些问题？
答：一直以来，我们对固有免疫系统如何识别病原体特异性组分的问题非常感兴趣，并且正在进行Toll样受体研究。我们曾报道了TLR7和TLR9分别是病毒单链RNA和DNA的受体。
TLR3被证实也能够识别病毒双链RNA。然而，正如论文中所揭示，发现TLR系统在体内抗病毒反应中并非必须。因此，我们对宿主在病毒识别和Ⅰ型干扰素的产生机制方面进行了研究。
编者按：本采访记录由丁香园网友迷北方的狼翻译。
编辑：西门吹血
作者: Hiroki Kato 等
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