GSE53806
Analysis of the mRNA Targetome of MicroRNAs Expressed by Marek’s Disease Virus
Marek’s disease virus 1 (MDV-1), an oncogenic -herpesvirus that induces T-cell lymphomas in chickens, serves as  model system to study transformation by lymphotropic herpesviruses. Like the oncogenic human  -herpesviruses Kaposi’s  sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), MDV-1 encodes several viral microRNAs (miRNAs). One  MDV-1 miRNA, miR-M4, shares the same “seed” targeting sequence with both a KSHV miRNA, miR-K11, and cellular miR-155.  Importantly, miR-M4 plays a critical role in T-cell transformation by MDV-1, while miR-K11 and cellular miR-155 are thought  to play key roles in B-cell transformation by KSHV and EBV, respectively. Here, we present an analysis of the mRNAs targeted by  viral miRNAs expressed in the chicken T-cell line MSB1, which is naturally coinfected with MDV-1 and the related nonpathogenic  virus MDV-2. Our analysis identified>1,000 endogenous mRNAs targeted by miRNAs encoded by each virus, many of  which are targeted by both MDV-1 and MDV-2 miRNAs. We present a functional analysis of an MDV-1 gene, RLORF8, targeted  by four MDV-1 miRNAs and a cellular gene, encoding interleukin-18 (IL-18) and targeted by both MDV-1 and MDV-2 miRNAs,  and show that ectopic expression of either protein in a form resistant to miRNA inhibition results in inhibition of cell proliferation.  Finally, we present a restricted list of 9 genes targeted by not only MDV-1 miR-M4 but also KSHV miR-K11 and human  miR-155. Given the critical role played by miR-155 seed family members in lymphomagenesis in humans and chickens, these  mRNA targets may contain genes whose inhibition plays a conserved role in herpesvirus transformation. Overall design: PAR-CLIP experiment of MSB1 cells