title: CD40 ligand is a critical effector of Epstein-Barr virus in host cell survival and transformation.
abstract: Epstein-Barr virus (EBV), implicated in numerous human diseases, including lymphoid malignancies, persistently infects peripheral B cells and transforms them into lymphoblastoid cell lines. Here we found that EBV equally infected B cells from patients with X-linked hyper IgM syndrome and those from healthy donors; however, it hardly transformed X-linked hyper IgM syndrome B cells, because of the dysfunctional gene of CD40 ligand (CD40L) of the patients. Unlike CD40, CD40L is not usually expressed on B cells. However, we found that EBV infection of normal B cells induced CD40L expression as a critical effector in host cell transformation and survival. Moreover, chronic active EBV infection of peripheral T cells, implicated in T cell malignancies, was associated with ectopic expression of CD40, and, in Jurkat T cells, EBV infection induced CD40 expression. These results suggest that EBV infection induces CD40L/CD40 signaling in host cells, which appears to play an essential role in its persistent infection and malignancies of lymphocytes.
authors.affiliation: Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Tokyo 113-8510, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Imadome
authors.forename: Masaki
authors.initials: M
authors.lastname: Shirakata
authors.forename: Norio
authors.initials: N
authors.lastname: Shimizu
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nonoyama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamanashi
mesh_terms: D017209:Apoptosis; D001402:B-Lymphocytes / Q000378:metabolism; D015139:Blotting, Southern; D019013:CD40 Antigens / Q000096:biosynthesis; D023201:CD40 Ligand / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D041321:Chromosomes, Human, X; D004247:DNA / Q000378:metabolism; D020031:Epstein-Barr Virus Infections; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism; D005434:Flow Cytometry; D008040:Genetic Linkage; D004854:Herpesvirus 4, Human / Q000378:metabolism*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D019169:Jurkat Cells; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000378:metabolism
chemical_list: D019013:CD40 Antigens; D019309:Epstein-Barr Virus Nuclear Antigens; D007075:Immunoglobulin M; D012333:RNA, Messenger; D023201:CD40 Ligand; D004247:DNA; C417029:EBV-encoded nuclear antigen 1