Critical Role of the Virus-Encoded MicroRNA-155 Ortholog in the Induction of Marek's Disease Lymphomas

• DOI: 10.1371/journal.ppat.1001305
• Publication Date: 2011-02-24T21:43:15Z
• Authors: Yuguang Zhao; Hongtao Xu; Yongxiu Yao; Lorraine P. Smith; Lydia Kgosana; James Green; Lawrence Petherbr...; Susan J. Baigent; Venugopal Nair
• Keywords: Marek's disease; Oncovirus; clone (Java method); Neoplastic transformation

Notwithstanding the well-characterised roles of a number oncogenes in neoplastic transformation, microRNAs (miRNAs) are increasingly implicated several human cancers. Discovery miRNAs oncogenic herpesviruses such as KSHV has further highlighted potential virus-encoded to contribute their capabilities. Nevertheless, despite identification possible cancer-related genes targets, direct vivo role diseases those induced by is difficult demonstrate absence suitable models. However, excellent natural disease models rapid-onset Marek's (MD) lymphomas chickens allow examination miRNAs. Using viruses modified reverse genetics infectious BAC clone RB-1B strain MDV, we show that deletion six-miRNA cluster 1 from viral genome abolished oncogenicity virus. This loss appeared be primarily due single miRNA within cluster, miR-M4, ortholog cellular miR-155, since its or 2-nucleotide mutation seed region was sufficient inhibit induction lymphomas. The definitive this miR-155 confirmed rescue phenotype revertant expressed either miR-M4 homolog gga-miR-155. first demonstration inducing tumors infection model. Furthermore, use deleted effective vaccines against virulent MDV challenge, enables prospects generating genetically defined attenuated vaccines.