Sifkarovski Jason, Grayfer Leon, De Jesús Andino Francisco, Lawrence B Paige, Robert Jacques
Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, USA.
Department of Environmental Medicine, University of Rochester Medical Center, Rochester, USA; Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, USA.
Dev Comp Immunol. 2014 Nov;47(1):52-8. doi: 10.1016/j.dci.2014.06.012. Epub 2014 Jun 28.
The recent dramatic increase of the prevalence and range of amphibian host species and populations infected by ranaviruses such as Frog Virus 3 (FV3) raises concerns about the efficacies of amphibian antiviral immunity. In this context, the potential negative effects of water contaminants such as the herbicide atrazine, at environmentally relevant levels, on host antiviral immunity remains unclear. Here we describe the use of the amphibian Xenopus laevis as an ecotoxicology platform to elucidate the consequences of exposure to ecologically relevant doses of atrazine on amphibian antiviral immunity. X. laevis were exposed at tadpole and adult stages as well as during metamorphosis to atrazine (range from 0.1 to 10.0 ppb) prior to infection with FV3. Quantitative analysis of gene expression revealed significant changes in the pro-inflammatory cytokine, TNF-α and the antiviral type I IFN gene in response to FV3 infection. This was most marked in tadpoles that were exposed to atrazine at doses as low 0.1 ppb. Furthermore, atrazine exposure significantly compromised tadpole survival following FV3 infections. In contrast, acute atrazine exposure of mature adult frogs did not induce detectable effects on anti-FV3 immunity, but adults that were exposed to atrazine during metamorphosis exhibited pronounced defects in FV3-induced TNF-α gene expression responses and slight diminution in type I IFN gene induction. Thus, even at low doses, atrazine exposure culminates in impaired development of amphibian antiviral defenses.
近期，诸如蛙病毒3（FV3）等蛙病毒感染的两栖动物宿主物种及种群的患病率和范围急剧增加，这引发了人们对两栖动物抗病毒免疫功效的担忧。在此背景下，诸如除草剂阿特拉津等水污染物在环境相关浓度下对宿主抗病毒免疫的潜在负面影响仍不明确。在此，我们描述了如何利用非洲爪蟾作为生态毒理学平台，以阐明暴露于生态相关剂量的阿特拉津对两栖动物抗病毒免疫的影响。在感染FV3之前，将非洲爪蟾的蝌蚪期、成年期以及变态期暴露于阿特拉津（浓度范围为0.1至10.0 ppb）。基因表达的定量分析显示，在感染FV3后，促炎细胞因子肿瘤坏死因子-α（TNF-α）和抗病毒I型干扰素基因发生了显著变化。这在暴露于低至0.1 ppb阿特拉津的蝌蚪中最为明显。此外，暴露于阿特拉津显著降低了FV3感染后蝌蚪的存活率。相比之下，对成年青蛙进行急性阿特拉津暴露并未对其抗FV3免疫产生可检测到的影响，但在变态期暴露于阿特拉津的成年青蛙在FV3诱导的TNF-α基因表达反应中表现出明显缺陷，且I型干扰素基因诱导略有减少。因此，即使在低剂量下，暴露于阿特拉津最终也会导致两栖动物抗病毒防御能力发育受损。
