Studies leading to sustainable strategies for the control of Marek's disease: Is vaccination responsible for virulence evolution in Marek's disease?

马立克氏病病毒是一种鸡的致癌病毒，每年造成全球10亿美元的损失，造成相当大的动物痛苦，并使自由放养的家禽经营和可能的野生动物处于危险之中。在商业家禽养殖中，该病毒在过去50年中已经进化出更强的毒力，以前从未见过的高致病性毒株现在正在传播。这些疫苗会迅速杀死未接种疫苗的鸟类。似乎极有可能是人们对MDV与鸡的相互作用所做的一些事情促使了这种病毒的进化;在这里，我们试图找出是什么。这对家禽业来说是一个重要的问题，需要评估未来MDV毒力的可能方向以及与替代控制策略（如新疫苗和基因增强鸡）相关的进化风险。从商业、道德和可能的野生动物保护角度来看，防止进一步的毒力进化，甚至逆转毒力进化，都是非常可取的。虽然MDV毒力进化已经发生，但对家禽业改变的环境条件中的哪一种是导致这种进化的原因几乎没有了解。一个主要的可能性是它是疫苗。自20世纪60年代末以来，MDV一直接受疫苗接种。MDV疫苗不具有消毒作用，因此接种疫苗的鸟类会传播从其环境中获得的病毒。这种“漏”的疫苗接种使病毒在免疫人群中的进化成为可能。理论模型表明，泄漏的疫苗可以促进毒力的增加;这里的直觉是，通过保护宿主，疫苗可以防止有毒病原体杀死宿主，从而杀死它们自己。因此，在它们以前被自然选择去除的地方，它们可以在接种疫苗的人群中传播。在本提案中，我们的目标是确定这种情况是否可以解释MDV毒力增加。实验工作将涉及不同毒力的MDV毒株在接种疫苗和未接种疫苗的禽类中的进化适应性的比较，以及通过接种疫苗和未接种疫苗的禽类的病毒毒株的实验进化。随后的数据将能够直接检验疫苗假说，以及MDV毒力进化的其他可能解释。这将直接有助于MDV管理，但更广泛地说，将决定是否有其他疾病-农业和人类-在这些疾病中，泄漏疫苗的广泛使用可能导致病原体菌株的进化，使未接种疫苗的人面临更大的风险。

Marek's disease virus is a cancer-causing virus of chickens which causes global losses of $US1 billion/year, considerable animal suffering, and which puts at risk free-range poultry operations and possibly wildlife. In commercial poultry operations, the virus has evolved substantially greater virulence over the last fifty years, with previously unseen hyperpathogenic strains now circulating. These rapidly kill unvaccinated birds. It seems extremely likely that something people did to the MDV-chicken interaction prompted this virus evolution; here we seek to find out what. This is an important issue for the poultry industry, which needs to assess the likely direction of future MDV virulence and the evolutionary risk associated with alternative control strategies such new vaccines and genetically enhanced chickens. Preventing further virulence evolution, and even reversing it, would be highly desirable on commercial, ethical and possibly wildlife conservation grounds. While there is little doubt that MDV virulence evolution has occurred, there is very little understanding of which of environmental conditions changed by the poultry industry has been responsible for this evolution. A leading possibility is that it is vaccination. MDV has been subject to vaccination since the late 1960's. MDV vaccines are not sterilising, so that vaccinated birds transmit virus they acquire from their environment. Such 'leaky' vaccination makes viral evolution in immunised populations possible. Theoretical models show that leaky vaccines can prompt virulence increases; the intuition here is that by protecting hosts, vaccines keep virulent pathogens from killing their hosts and therefore themselves. Thus, where they would previously have been removed by natural selection, they can circulate in vaccinated populations. In this proposal, we aim to determine whether this scenario can explain MDV virulence increases. The experimental work will involve comparisons of the evolutionary fitness of MDV strains of varying virulence in vaccinated and unvaccinated birds, and experimental evolution of viral strains through vaccinated and unvaccinated birds. The subsequent data will enable direct testing of the vaccine hypothesis, and other possible explanations of MDV virulence evolution. This will directly contribute to MDV management, but more broadly, will determine whether there are other diseases - agricultural and human - where widespread use of leaky vaccines could lead to the evolution of pathogen strains which put the unvaccinated at greater risk.