Prominent Amphibian (Xenopus laevis) Tadpole Type III Interferon Response to the Frog Virus 3 Ranavirus
Prominent Amphibian (Xenopus laevis) Tadpole Type III Interferon Response to the Frog Virus 3 Ranavirus
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DOI：
10.1128/jvi.00051-15
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发表时间：
2015-05-01
影响因子：
5.4
通讯作者：
Robert, Jacques
中科院分区：
文献类型：
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作者：
Grayfer, Leon;Andino, Francisco De Jess;Robert, Jacques
蛙病毒（虹彩病毒科）对两栖动物种群构成越来越大的威胁，无尾类蝌蚪对这些病毒感染特别敏感。此外，两栖动物是已知具有I型和III型干扰素（IFN）介导的免疫力的脊椎动物中最基本的系统发育类。此外，很少有人知道有关的IFN介质在两栖类抗病毒防御各自的作用。因此，我们在转录和功能上比较了两栖动物非洲爪蟾I型（IFN）和III型（IFN-λ）IFN在蛙病毒蛙病毒3（FV 3）感染的背景下。X.非洲乳杆菌IFN和IFN-λ显示不同的组织表达谱。与我们之前的发现X.与成年蝌蚪的反应相比，非洲蟾蜍蝌蚪对FV 3感染表现出延迟的和适度的I型IFN反应，在这里，我们报道了蝌蚪对III型IFN基因的反应。这些细胞因子的重组形式（重组X. Iaevis IFN [rX 1 IFN]和rX 1 IFN-λ）在肾衍生的A6细胞系以及蝌蚪白细胞和组织中引发抗病毒基因表达。然而，rXlIFN-λ在防止A6细胞和蝌蚪中的FV 3复制方面不如rXlIFN有效，并且在促进蝌蚪存活方面不如rXlIFN。有趣的是，FV 3损害A6细胞和蝌蚪肾III型IFN受体基因表达。此外，在A6培养物中，rX 1 IFN-λ赋予与rX 1 IFN相等或更大的保护，以对抗缺乏推定的免疫逃避基因、病毒半胱天冬酶活化和募集结构域（vCARD）或截短的vIF-2 α基因的重组病毒。因此，与先前的假设相反，蝌蚪具有依赖于III型IFN的完整的抗病毒防御，其被FV 3病原体所克服。重要无尾类蝌蚪，包括非洲爪蟾的蝌蚪，特别容易受到诸如FV 3的蛙病毒的感染。我们研究了X的各自作用。FV 3感染期间的羊I型和III型干扰素（分别为IFN和IFN-λ）。值得注意的是，蝌蚪安装及时和更强大的IFN-λ基因表达反应FV 3比成人，与穷人的蝌蚪I型IFN反应。然而，重组X. laevis IFN-λ（rX 1 IFN-λ）对蝌蚪和A6细胞系的保护作用低于rX 1 IFN，这可以通过FV 3损伤IFN-λ受体基因表达来解释。IFN-λ在蝌蚪抗FV 3防御中的重要性通过两个假定的免疫逃避基因在FV 3对IFN-和IFN-λ介导的应答的抗性中的关键参与而被强调。这些发现挑战了蝌蚪具有缺陷的抗病毒免疫力的观点，并表明，相反，它们的抗病毒反应主要是由IFN-λ反应，这是克服了FV 3。
Ranaviruses (Iridoviridae) are posing an increasing threat to amphibian populations, with anuran tadpoles being particularly susceptible to these viral infections. Moreover, amphibians are the most basal phylogenetic class of vertebrates known to possess both type I and type III interferon (IFN)-mediated immunity. Moreover, little is known regarding the respective roles of the IFN mediators in amphibian antiviral defenses. Accordingly, we transcriptionally and functionally compared the amphibian Xenopus laevis type I (IFN) and III (IFN-lambda) IFNs in the context of infections by the ranavirus frog virus 3 (FV3). X. laevis IFN and IFN-lambda displayed distinct tissue expression profiles. In contrast to our previous findings that X. laevis tadpoles exhibit delayed and modest type I IFN responses to FV3 infections compared to the responses of adults, here we report that tadpoles mount timely and robust type III IFN gene responses. Recombinant forms of these cytokines (recombinant X. laevis IFN [rXlIFN] and rXlIFN-lambda) elicited antiviral gene expression in the kidney-derived A6 cell line as well as in tadpole leukocytes and tissues. However, rXlIFN-lambda was less effective than rXlIFN in preventing FV3 replication in A6 cells and tadpoles and inferior at promoting tadpole survival. Intriguingly, FV3 impaired A6 cell and tadpole kidney type III IFN receptor gene expression. Furthermore, in A6 cultures rXlIFN-lambda conferred equal or greater protection than rXlIFN against recombinant viruses deficient for the putative immune evasion genes, the viral caspase activation and recruitment domain (vCARD) or a truncated vIF-2 alpha gene. Thus, in contrast to previous assumptions, tadpoles possess intact antiviral defenses reliant on type III IFNs, which are overcome by FV3 pathogens.IMPORTANCEAnuran tadpoles, including those of Xenopus laevis, are particularly susceptible to infection by ranavirus such as FV3. We investigated the respective roles of X. laevis type I and type III interferons (IFN and IFN-lambda, respectively) during FV3 infections. Notably, tadpoles mounted timely and more robust IFN-lambda gene expression responses to FV3 than adults, contrasting with the poorer tadpole type I IFN responses. However, a recombinant X. laevis IFN-lambda (rXlIFN-lambda) conferred less protection to tadpoles and the A6 cell line than rXlIFN, which may be explained by the FV3 impairment of IFN-lambda receptor gene expression. The importance of IFN-lambda in tadpole anti-FV3 defenses is underlined by the critical involvement of two putative immune evasion genes in FV3 resistance to IFN- and IFN-lambda-mediated responses. These findings challenge the view that tadpoles have defective antiviral immunity and suggest, rather, that their antiviral responses are predominated by IFN-lambda responses, which are overcome by FV3.