title: Role of latent membrane protein 1 in chronic active Epstein-Barr virus infection-derived T/NK-cell proliferation.
abstract: Epstein-Barr virus (EBV) predominantly infects B cells and causes B-cell lymphomas, such as Burkitt lymphoma and Hodgkin lymphoma. However, it also infects other types of cells, including T and natural killer (NK) cells, and causes disorders, such as chronic active EBV infection (CAEBV) and T/NK-cell lymphoma. The CAEBV is a lymphoproliferative disease with poor prognosis, where EBV-positive T or NK cells grow rapidly, although the molecular mechanisms that cause the cell expansion still remain to be elucidated. EBV-encoded latent membrane protein 1 (LMP1) is an oncogene that can transform some cell types, such as B cells and mouse fibroblasts, and thus may stimulate cell proliferation in CAEBV. Here, we examined the effect of LMP1 on EBV-negative cells using the cells conditionally expressing LMP1, and on CAEBV-derived EBV-positive cells by inhibiting the function of LMP1 using a dominant negative form of LMP1. We demonstrated that LMP1 was responsible for the increased cell proliferation in the cell lines derived from CAEBV, while LMP1 did not give any proliferative advantage to the EBV-negative cell line.
authors.affiliation: Department of Virology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.
authors.forename: Takuto
authors.initials: T
authors.lastname: Ito
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Kawazu
authors.forename: Takayuki
authors.initials: T
authors.lastname: Murata
authors.forename: Seiko
authors.initials: S
authors.lastname: Iwata
authors.forename: Saki
authors.initials: S
authors.lastname: Arakawa
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Sato
authors.forename: Kiyotaka
authors.initials: K
authors.lastname: Kuzushima
authors.forename: Fumi
authors.initials: F
authors.lastname: Goshima
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kimura
mesh_terms: D017209:Apoptosis; D049109:Cell Proliferation; D002908:Chronic Disease; D020031:Epstein-Barr Virus Infections / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D019169:Jurkat Cells; D055611:Natural Killer T-Cells / Q000276:immunology / Q000378:metabolism*; D014763:Viral Matrix Proteins / Q000502:physiology*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins
keywords: AKT; CAEBV; LMP1; NFκB; dominant negative