Functional analysis of novel microRNAs encoded by avian herpesviruses

马立克氏病(MD)是鸡的一种常见疾病，涉及瘫痪，通常死于高度恶性T淋巴瘤(白血球癌症)的生长。马立克氏病是由一种传播性病原体--马立克氏病病毒引起的。MDV具有很强的传染性，是全球家禽业的主要威胁。目前，它是通过接种疫苗来控制的，每年使用近220亿剂疫苗试图控制这种疾病。尽管如此，病毒仍在不断向更强的毒力进化，因此有必要在前一代疫苗失效时，每隔8-10年定期推出新疫苗。这种病毒获得毒力并产生肿瘤的机制仍然知之甚少。在过去的两年里，在BBSRC的资金支持下，我们一直在研究由病毒和宿主编码的称为microRNAs(小22核苷酸长RNA分子)的新型调控分子在诱发MD中的作用。作为这笔赠款的一部分，我们已经在马迪乌斯属3个成员的基因组中鉴定了几个新的microRNAs。初步研究表明，在MDV诱导的癌细胞中，这些小分子的产生水平非常高，它们从病毒基因组中的缺失影响了它们产生肿瘤的能力。在这项旨在建立在我们工作发现的基础上的提案中，我们希望继续我们的研究，以确定病毒编码的miRNAs靶向的分子，并检查从这些病毒的基因组中删除这些microRNAs的效果。

Marek's disease (MD) is a common disease of chickens involving paralysis and commonly death from the growth of highly malignant T lymphomas (cancers of white blood cells). MD is caused by a transmissible agent, Marek's disease virus (MDV). MDV is very contagious and is a major threat to the poultry industry worldwide. Presently, it is controlled by vaccination, and nearly 22 billion vaccine doses a year are used in an attempt to control the disease. Despite this, there is a continuous evolution of the virus towards greater virulence necessitating the introduction of new vaccines at regular intervals of 8-10 years when the previous generation of vaccine becomes ineffective. The mechanisms by which the virus gains virulence and produces tumours remain very poorly understood. During the last 2 years, with the financial support from the BBSRC, we have been examining the role of novel regulatory molecules called microRNAs (small 22-nucleotide long RNA molecules) encoded by the virus and the host in inducing MD. As part of this grant, we have identified several novel microRNAs in the genome of the 3 members of the genus Mardivirus. Preliminary studies have indicated that these tiny molecules are produced at very high levels in MDV-induced cancer cells and their deletion from the virus genome affected their ability to produce tumours. In this proposal, which is aimed to build on the findings of our work, we want to continue our research to identify the molecules targeted by the virus-encoded miRNAs and examine the effect of deleting these microRNAs from the genomes of these viruses.