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【Fast Breaking Comments】Cell type-specific involvement of

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

A:

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
screen.width-333)this.width=screen.width-333" width=250 height=157 title="Click to view full june06-Takeuchi_Kato_Akira.jpg (250 X 157)" border=0 align=absmiddle> 问:为什么你认为你的论文有很高的引用率?
答:病毒学家们对宿主如何识别RNA病毒以及抗病毒反应是如何激发的这些问题进行了多年的研究。对病毒组分如双链RNA(dsRNA)的识别能迅速诱导I型干扰素和前炎性细胞因子的释放。最新的研究表明,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,目前还不清楚对病毒的识别在体内如何引起宿主的抗病毒反应。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的RNA病毒识别过程中的重要作用。与此相对的,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的表达中的重要作用。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的有价值的工具。

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作者:admin@医学,生命科学    2011-02-27 05:11
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