title: Epstein-Barr nuclear antigen 1 induces expression of the cellular microRNA hsa-miR-127 and impairing B-cell differentiation in EBV-infected memory B cells. New insights into the pathogenesis of Burkitt lymphoma.
abstract: Epstein-Barr Virus (EBV) is a γ-herpesvirus that infects >90% of the human population. Although EBV persists in its latent form in healthy carriers, the virus is also associated with several human cancers. EBV is strongly associated with Burkitt lymphoma (BL), even though there is still no satisfactory explanation of how EBV participates in BL pathogenesis. However, new insights into the interplay between viruses and microRNAs (miRNAs) have recently been proposed. In particular, it has been shown that B-cell differentiation in EBV-positive BL is impaired at the post-transcriptional level by altered expression of hsa-miR-127. Here, we show that the overexpression of hsa-miR-127 is due to the presence of the EBV-encoded nuclear antigen 1 (EBNA1) and give evidence of a novel mechanism of direct regulation of the human miRNA by this viral product. Finally, we show that the combinatorial expression of EBNA1 and hsa-miR-127 affects the expression of master B-cell regulators in human memory B cells, confirming the scenario previously observed in EBV-positive BL primary tumors and cell lines. A good understanding of these mechanisms will help to clarify the complex regulatory networks between host and pathogen, and favor the design of more specific treatments for EBV-associated malignancies.
authors.affiliation: Department of Human Pathology and Oncology, University of Siena, Siena, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Onnis
authors.forename: M
authors.initials: M
authors.lastname: Navari
authors.forename: G
authors.initials: G
authors.lastname: Antonicelli
authors.forename: F
authors.initials: F
authors.lastname: Morettini
authors.forename: S
authors.initials: S
authors.lastname: Mannucci
authors.forename: G
authors.initials: G
authors.lastname: De Falco
authors.forename: E
authors.initials: E
authors.lastname: Vigorito
authors.forename: L
authors.initials: L
authors.lastname: Leoncini