Latent membrane protein 1 of Epstein Barr Virus alters cellular microRNAs in B cell lymphomas (169.37)

Abstract

Abstract Epstein-Barr Virus (EBV) infection is usually benign but immunodeficiency can lead to B cell lymphomas such as Post-Transplant Lymphoproliferative Disease (PTLD). PTLD is associated the expression of the EBV oncogene latent membrane protein 1 (LMP1). MicroRNAs (miRs) are small, non-coding RNAs that regulate gene expression. We hypothesized that LMP1 signaling in EBV+ B cell lymphomas can modulate cellular miRNA expression as a mechanism to promote viral persistence and/or host cell survival. Using an inducible, chimeric LMP1 signaling system we analyzed miR expression in a B cell lymphoma cell line after activation of LMP1 variants isolated from PTLD patients and from the B95.8 form obtained from a mononucleosis patient. The expression of 747 miRs was assayed by qPCR array and 323 miRs were detected. B95.8 LMP1 activation modulated 50 total miRs including miR503, linked to inhibition of proliferation in epithelial cells. The PTLD-derived LMP1 variants modulated 59 distinct miRs. These included pro-apoptotic miR29b which was down-regulated by PTLD-derived LMP1 variants but not by B95.8 LMP1. These data indicate that PTLD-derived forms of LMP1 uniquely alter cellular miR as compared to B95.8 LMP1. Thus, study of the functional properties of LMP1 variants may provide insight into mechanisms of lymphomagenesis.