Marek's disease virus spread: In and out of chickens

马立克氏病(MD)是由马立克氏病病毒(MDV)引起的一种高度传染性的禽类淋巴瘤，是一种严重影响养鸡业的甲型疱疹病毒。尽管在过去40年中广泛使用减毒活疫苗，马立克氏病仍然是家禽生产的主要威胁，全球每年的经济损失估计在10亿美元左右。在欧洲和其他国家，MDV已经演变成在较新的毒株中观察到的毒力大幅增加，从而威胁到当前疫苗接种战略的可持续性。这种疾病的地方性特征显然与病毒传播方式和现有疫苗提供的不完全保护有关。众所周知，虽然疫苗可以预防这种疾病，但感染和病毒传播并未停止。我们假设，在接种疫苗的禽类中，致病毒株的持久性和鸟对鸟的传播为出现非常毒力的毒株提供了基础。MDV的成功传播需要在接种疫苗和未接种疫苗的禽类中有效地从受感染的禽类中脱落病毒，并通过呼吸道途径进入病毒。提高对病毒复制这两个基本步骤的了解，对于最终减少MDV对环境的污染和对动物的感染至关重要。到目前为止，与病毒诱导的肿瘤发生、宿主抗性和毒力相比，MDV在体内的进入和排出的研究很少。我们的项目旨在研究细胞和分子水平上参与病毒进入和排出的关键元件。我们项目的创新之处在于关注分化细胞，分化细胞代表体内感染的主要靶细胞，来自造血系(巨噬细胞和淋巴细胞)或来自皮肤上皮。

Marek's disease (MD) is a highly contagious virus-induced lymphoma in poultry caused by Marek's disease virus (MDV), an alphaherpesvirus heavily affecting chicken industry. In spite of the widespread use of live attenuated vaccines during the last 40 years, MD remains a major threat for poultry production with estimated annual economic losses in the range of 1 billion dollars worldwide. In Europe as well as in other countries, MDV has evolved towards a substantially increased virulence observed in more recent strains, thereby threatening the sustainability of the current vaccination strategy. The endemic nature of the disease is clearly linked to the mode of virus transmission and to incomplete protection provided by current vaccines. It is well known that while vaccines protect against the disease, infection and virus shedding are not halted. We hypothesize that the persistence and bird-to-bird transmission of pathogenic strains in vaccinated birds provide the basis for the emergence of very virulent strains. Successful transmission of MDV entails efficient viral shedding from infected birds and the entry of the virus via the respiratory route, in both vaccinated and naïve birds. Improved knowledge about these two essential steps in virus replication is critical to ultimately reduce MDV contamination of the environment and infection of the animals. To date, entry and shedding of MDV in vivo have been poorly studied compared to virus-induced tumourigenesis, host resistance and virulence. Our project aims to study the key elements on the cellular and molecular levels that are involved in virus entry and shedding. The novelty of our project is to focus on differentiated cells, which represent the major target cells infected in vivo and are derived either from the haematopoeitic lineage (macrophages and lymphocytes) or from the skin epithelium.