Galleria mellonella as an infection model for viral pathogens

(Galleria Mellonella)蜡蛾幼虫现在被实验室用来研究由真菌和细菌病原体引起的疾病。这是用替代的和更符合道德的替代品取代哺乳动物实验的倡议的伟大成功故事之一。去年有231家出版物使用这种模式，而2017年和2016年分别为194家和141家。蜡蛾幼虫模型现在被用来研究真菌和细菌致病的方式，并测试用药物治疗这些疾病的新方法。蜡蛾幼虫之所以得到如此广泛的使用，有几个原因。首先，它们的免疫系统类似于哺乳动物免疫系统的一部分，因此它们比细胞培养模型更有效地模拟疾病过程。第二，与许多无脊椎动物不同，它们可以保持在37摄氏度。最后，它们足够大，易于处理，可以注射准确剂量的微生物和药物。然而，蜡蛾幼虫对病毒引起的疾病的研究还没有报道。在一定程度上，这反映了人们对病毒具有很强的宿主特异性的认识。但我们也意识到，一些病毒可以同时感染昆虫和哺乳动物。例如，许多病毒通过蚊子和扁虱传播，并在人类和其他哺乳动物中引起疾病。此外，有证据表明，当这些病毒感染昆虫时，它们可能会产生有害影响。对于这些病毒，用昆虫来研究感染可能是可行的。在这个简短而集中的项目中，我们将开展一项研究，以调查一系列昆虫传播的病毒是否会导致蜡蛾幼虫患病。我们已经进行了一项初步研究，表明一种名为委内瑞拉马脑脊髓炎(VEE)病毒的病毒会导致蜡蛾幼虫患病。我们将扩大我们对VEE病毒的初步研究，并测试相关病毒是否会导致蜡蛾幼虫患病。这将为使用这种模型来取代哺乳动物的实验提供机会。如果成功，我们估计50%的使用哺乳动物的实验可以被使用梅隆杆菌幼虫的研究所取代。此外，通过对蜡蛾幼虫进行初步研究，任何后续哺乳动物研究的设计都将得到改进，这些实验的价值也将得到提高。我们的工作将激励其他研究人员调查其他病毒是否能够在蜡蛾幼虫中致病，从而进一步应用该模型，并进一步减少动物在病毒研究中的使用。

(Galleria mellonella) waxmoth larvae are now being used by laboratories to study diseases caused by fungal and bacterial pathogens. It has been one of the great success stories of the initiatives to replace experiments with mammals with alternative and more ethical alternatives. Last year there were 231 publications using this model, compared to 194 publications and 2017 and 141 publications in 2016. The waxmoth larvae model is now used to study the ways in which fungi and bacteria cause disease and to test new ways of treating the diseases with drugs. There are several reasons why waxmoth larvae have become so widely used. First, they have an immune system, which resembles parts of the mammalian immune system, so they mimic the disease process much more effectively than, for example, cell culture models. Second, unlike many invertebrates they can be kept at 37oC. Finally, they are large enough to be handled easily and to be injected with exact doses of the microorganism and drugs. However, waxmoth larvae have not yet been reported to be of value for the study of diseases caused by viruses. In part, this reflects the knowledge that viruses are very host-specific. But we are also aware that some viruses can infect both insects and mammals. For example, many viruses are spread by mosquitos and ticks and cause disease in human and other mammals. Moreover, there is evidence that when these viruses infect insects they can have detrimental effects. For these viruses it may be feasible to use insects to study the infections. In this short and focussed project we will carry out a study to investigate whether a range of insect-borne viruses can cause disease in waxmoth larvae. We have already carried out a pilot study indicating that a virus called Venezuelan Equine Encephalomyelitis (VEE) virus causes disease in waxmoth larvae. We will extend our pilot study with VEE virus and also test whether related viruses can cause disease in waxmoth larvae. This would then open up opportunities to use this model to replace experiments with mammals. If successful, we estimate that 50% of experiments using mammals could be replaced with studies using G. mellonella larvae. In addition, by carrying out preliminary studies in waxmoth larvae the design of any subsequent studies in mammals would be refined and the value of these experiments improved. Our work will stimulate other researchers to investigate whether other viruses are able to cause disease in waxmoth larvae allowing for further application of the model and a further reduction of animal use in the study of viruses.