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Human Monocytic Cell Lines Transformed In Vitro by Epstein-Barr Virus Display a Type II Latency and LMP-1-Dependent Proliferation
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Edité par CCSD ; American Society for Microbiology -
International audience. Epstein-Barr virus (EBV) classically infects and transforms B lymphocytes in vitro, yielding lymphoblastoidcell 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 expres-sion. In the present study, we report the characterization of E1, a monocytic cell line infected and transformedby EBV. This cell line was derived from an LCL by a drastic electroporation and selection of neomycin-resistantcells, unfavorable to B-cell outgrowth. E1 expressed surface molecules of monocytic lineage (CD14, majorhistocompatibility complex class II, and CD80) and the c-fms gene, a highly specific marker for the monocyticlineage. This cell line is able to phagocytose and secrete proinflammatory monokines tumor necrosis factoralpha, interleukin-6 (IL-6), and IL-8. E1 cells are tumorigenic after injection in nude mice, and a monocyticcell line obtained from one of these tumors (TE1) displayed immunophenotype and functional propertiessimilar to those of E1. We detected the presence of the EBV genome in both cell lines, as well as expression ofthe EBNA-1 and LMP-1, but not EBNA-2, viral genes, characteristic of a type II latency. LMP-1 influences thephenotype of these monocytic cell lines, as demonstrated by down-regulation of cell proliferation and mem-brane intercellular adhesion molecule 1 expression due to an LMP-1 antisense strategy. This is the firstdescription of a latently infected human monocytic cell line and the first direct demonstration of an instru-mental role for LMP-1 in the proliferation of EBV-transformed cell lines expressing a type II latency.
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