title: Human monocytic cell lines transformed in vitro by Epstein-Barr virus display a type II latency and LMP-1-dependent proliferation.
abstract: Epstein-Barr virus (EBV) classically infects and transforms B lymphocytes in vitro, yielding lymphoblastoid cell lines (LCLs). In contrast to other herpesviruses, EBV is not described as an infectious agent for monocytes. However, recent papers described in vitro infection of monocytes leading to abortive or transient viral expression. In the present study, we report the characterization of E1, a monocytic cell line infected and transformed by EBV. This cell line was derived from an LCL by a drastic electroporation and selection of neomycin-resistant cells, unfavorable to B-cell outgrowth. E1 expressed surface molecules of monocytic lineage (CD14, major histocompatibility complex class II, and CD80) and the c-fms gene, a highly specific marker for the monocytic lineage. This cell line is able to phagocytose and secrete proinflammatory monokines tumor necrosis factor alpha, interleukin-6 (IL-6), and IL-8. E1 cells are tumorigenic after injection in nude mice, and a monocytic cell line obtained from one of these tumors (TE1) displayed immunophenotype and functional properties similar to those of E1. We detected the presence of the EBV genome in both cell lines, as well as expression of the EBNA-1 and LMP-1, but not EBNA-2, viral genes, characteristic of a type II latency. LMP-1 influences the phenotype of these monocytic cell lines, as demonstrated by down-regulation of cell proliferation and membrane intercellular adhesion molecule 1 expression due to an LMP-1 antisense strategy. This is the first description of a latently infected human monocytic cell line and the first direct demonstration of an instrumental role for LMP-1 in the proliferation of EBV-transformed cell lines expressing a type II latency.
authors.affiliation: UMR 8527, CNRS/Lille II/Institut Pasteur de Lille, Institut de Biologie de Lille, 1 rue Calmette, 59021 Lille Cedex, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Masy
authors.forename: Eric
authors.initials: E
authors.lastname: Adriaenssens
authors.forename: Claire
authors.initials: C
authors.lastname: Montpellier
authors.forename: Pascale
authors.initials: P
authors.lastname: Crépieux
authors.forename: Alexandra
authors.initials: A
authors.lastname: Mougel
authors.forename: Brigitte
authors.initials: B
authors.lastname: Quatannens
authors.forename: Gautier
authors.initials: G
authors.lastname: Goormachtigh
authors.forename: Nathalie
authors.initials: N
authors.lastname: Faumont
authors.forename: Fabienne
authors.initials: F
authors.lastname: Meggetto
authors.forename: Claude
authors.initials: C
authors.lastname: Auriault
authors.forename: Hervé
authors.initials: H
authors.lastname: Groux
authors.forename: Jean
authors.initials: J
authors.lastname: Coll
mesh_terms: D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D018925:Chemokines / Q000096:biosynthesis; D020031:Epstein-Barr Virus Infections / Q000821:virology; D004854:Herpesvirus 4, Human / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D051379:Mice; D009000:Monocytes / Q000502:physiology* / Q000637:transplantation / Q000821:virology*; D010587:Phagocytosis; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014763:Viral Matrix Proteins / Q000378:metabolism*; D017735:Virus Latency
chemical_list: D018925:Chemokines; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D016186:Receptor, Macrophage Colony-Stimulating Factor