Levraud Jean-Pierre, Boudinot Pierre, Colin Ingrid, Benmansour Abdenour, Peyrieras Nadine, Herbomel Philippe, Lutfalla Georges
Macrophages et Développement de l'Immunité, Centre National de la Recherche Scientifique, Institut Pasteur, Paris, France.
J Immunol. 2007 Apr 1;178(7):4385-94. doi: 10.4049/jimmunol.178.7.4385.
The recent description of virus-induced fish IFNs has raised questions about the evolution of this complex antiviral system. Identification of the receptor of the zebrafish virus-induced IFN (zIFN) was sought to help resolve these questions. We set up an experimental system to study the zIFN system in the course of a viral infection of zebrafish embryos. In this setting, zIFN was induced by viral infection, and we identified zIFN-dependent induced transcripts. Embryos quickly died from the infection, but zIFN overexpression increased their survival. We took advantage of this experimental system to perform in vivo loss and gain of function analysis of candidate receptors of the class II helical receptor family and identified zCRFB1 and zCRFB5 as the two subunits of the zebrafish IFN receptor. Based on the organization of the zIFN gene and the protein structure of the identified receptor components, the virus-induced fish IFNs appear as orthologs of mammalian IFN-lambda, specifying type III IFN as the ancestral antiviral system of vertebrates.
最近对病毒诱导的鱼类干扰素的描述引发了关于这一复杂抗病毒系统进化的问题。为了帮助解决这些问题，人们试图鉴定斑马鱼病毒诱导干扰素（zIFN）的受体。我们建立了一个实验系统，以研究斑马鱼胚胎病毒感染过程中的zIFN系统。在这种情况下，病毒感染诱导产生zIFN，我们鉴定出了zIFN依赖性诱导转录本。胚胎很快死于感染，但zIFN的过表达提高了它们的存活率。我们利用这个实验系统对II类螺旋受体家族的候选受体进行体内功能缺失和功能获得分析，并鉴定出zCRFB1和zCRFB5是斑马鱼干扰素受体的两个亚基。基于zIFN基因的组织和所鉴定受体成分的蛋白质结构，病毒诱导的鱼类干扰素似乎是哺乳动物干扰素λ的直系同源物，这表明III型干扰素是脊椎动物的原始抗病毒系统。
