title: Epstein-Barr virus maintains lymphomas via its miRNAs.
abstract: Epstein-Barr virus (EBV) has evolved exquisite controls over its host cells, human B lymphocytes, not only directing these cells during latency to proliferate and thereby expand the pool of infected cells, but also to survive and thereby persist for the lifetime of the infected individual. Although these activities ensure the virus is successful, they also make the virus oncogenic, particularly when infected people are immunosuppressed. Here we show, strikingly, that one set of EBV's microRNAs (miRNAs) both sustain Burkitt's lymphoma (BL) cells in the absence of other viral oncogenes and promote the transformation of primary B lymphocytes. BL cells were engineered to lose EBV and found to die by apoptosis and could be rescued by constitutively expressing viral miRNAs in them. Two of these EBV miRNAs were found to target caspase 3 to inhibit apoptosis at physiological concentrations.
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: D T
authors.initials: DT
authors.lastname: Vereide
authors.affiliation: 1] Research Unit Gene Vectors, DZIF German Centre for Infection Research, Munich, Munich, Germany [2] Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Seto
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: Y-F
authors.initials: YF
authors.lastname: Chiu
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: M
authors.initials: M
authors.lastname: Hayes
authors.affiliation: 1] Research Unit Gene Vectors, DZIF German Centre for Infection Research, Munich, Munich, Germany [2] Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Tagawa
authors.affiliation: Heinrich-Pette-Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Grundhoff
authors.affiliation: 1] Research Unit Gene Vectors, DZIF German Centre for Infection Research, Munich, Munich, Germany [2] Helmholtz Zentrum München, German Research Center for Environmental Health, Munich, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Hammerschmidt
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, Madison, WI, USA.
authors.forename: B
authors.initials: B
authors.lastname: Sugden
mesh_terms: D017209:Apoptosis; D001402:B-Lymphocytes / Q000201:enzymology / Q000502:physiology / Q000821:virology; D001483:Base Sequence; D001665:Binding Sites; D002051:Burkitt Lymphoma / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference
chemical_list: D019309:Epstein-Barr Virus Nuclear Antigens; D035683:MicroRNAs; C505407:CASP3 protein, human; D053148:Caspase 3; C417029:EBV-encoded nuclear antigen 1