critical role of the virus-encoded microrna-155 ortholog in the induction of mareks disease lymphomas关键作用的微rna病毒编码的感应- 155直接同源马立克氏病淋巴瘤.pdfVIP

Critical Role of the Virus-Encoded MicroRNA-155 Ortholog in the Induction of Marek’s Disease Lymphomas 1 2 2 2 2 2 Yuguang Zhao , Hongtao Xu , Yongxiu Yao , Lorraine P. Smith , Lydia Kgosana , James Green , 2 2 2 Lawrence Petherbridge , Susan J. Baigent , Venugopal Nair * 1The Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, Oxford University, Oxford, United Kingdom, 2 Avian Oncogenic Virus Group, Avian Infectious Disease Programme, Institute for Animal Health, Berkshire, United Kingdom Abstract Notwithstanding the well-characterised roles of a number of oncogenes in neoplastic transformation, microRNAs (miRNAs) are increasingly implicated in several human cancers. Discovery of miRNAs in several oncogenic herpesviruses such as KSHV has further highlighted the potential of virus-encoded miRNAs to contribute to their oncogenic capabilities. Nevertheless, despite the identification of several possible cancer-related genes as their targets, the direct in vivo role of virus-encoded miRNAs in neoplastic diseases such as those induced by KSHV is difficult to demonstrate in the absence of suitable models. However, excellent natural disease models of rapid-onset Marek’s disease (MD) lymphomas in chickens allow examination of the oncogenic potential of virus-encoded miRNAs. Using viruses modified by reverse genetics of the infectious BAC clone of the oncogenic RB-1B strain of MDV, we show that the deletion of the six-miRNA cluster 1 from the viral genome abolished the oncogenicity of the virus. This loss of oncogenicity appeared to be primarily due to the single miRNA within the cluster, miR-M4, the ortholog of cellular miR-155, since its delet