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致癌性的鸡病毒，每年在全球造成10亿美元的损失，造成相当大的动物痛苦，并危及散养家禽养殖业，甚至可能危及野生动物。在商业家禽养殖中，该病毒在过去五十年中已经进化出更大的毒力，以前未见过的高致病性毒株现在正在流行。这些病毒会迅速杀死未接种疫苗的禽类。似乎极有可能是人们对mdv与鸡的相互作用所做的某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问题，需要评估未来MDV毒力的可能方向，以及与新疫苗和基因改良鸡等替代控制策略相关的进化风险。从商业、伦理和可能的野生动物保护的角度来看，阻止毒性进一步进化，甚至逆转它将是非常可取的。虽然毫无疑问，MDV的毒力进化已经发生，但对于家禽业改变的哪种环境条件导致了这种进化，人们知之甚少。一个主要的可能性是疫苗接种。自20世纪60年代末以来，MDV一直是接种疫苗的对象。MDV疫苗不能消毒，因此接种疫苗的禽类会传播它们从环境中获得的病毒。这种“漏洞”疫苗接种使病毒在免疫人群中进化成为可能。理论模型表明，有漏洞的疫苗可以促使毒力增加；这里的直觉是，通过保护宿主，疫苗可以防止毒性病原体杀死宿主，从而防止它们自己。因此，在它们以前被自然选择清除的地方，它们可以在接种疫苗的人群中传播。在这项提议中，我们的目标是确定这种情况是否可以解释MDV毒力增加。实验工作将包括比较不同毒力的MDV毒株在接种疫苗和未接种疫苗的鸟类中的进化适应性，以及在接种疫苗和未接种疫苗的鸟类中进行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，以及对MDV毒力演变的其他可能解释。这将直接有助于MDV的管理，但更广泛地说，将决定是否存在其他疾病——农业和人类——在这些疾病中，广泛使用有漏洞的疫苗可能导致病原体菌株的进化，从而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.