title: Activation of the B cell antigen receptor triggers reactivation of latent Kaposi's sarcoma-associated herpesvirus in B cells.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic herpesvirus and the cause of Kaposi's sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman's disease. Latently infected B cells are the main reservoir of this virus in vivo, but the nature of the stimuli that lead to its reactivation in B cells is only partially understood. We established stable BJAB cell lines harboring latent KSHV by cell-free infection with recombinant virus carrying a puromycin resistance marker. Our latently infected B cell lines, termed BrK.219, can be reactivated by triggering the B cell receptor (BCR) with antibodies to surface IgM, a stimulus imitating antigen recognition. Using this B cell model system we studied the mechanisms that mediate the reactivation of KSHV in B cells following the stimulation of the BCR and could identify phosphatidylinositol 3-kinase (PI3K) and X-box binding protein 1 (XBP-1) as proteins that play an important role in the BCR-mediated reactivation of latent KSHV.
authors.affiliation: Institute of Virology, Hanover Medical School, Hanover, Germany.
authors.forename: Semra
authors.initials: S
authors.lastname: Kati
authors.forename: Edward H
authors.initials: EH
authors.lastname: Tsao
authors.forename: Thomas
authors.initials: T
authors.lastname: Günther
authors.forename: Magdalena
authors.initials: M
authors.lastname: Weidner-Glunde
authors.forename: Thomas
authors.initials: T
authors.lastname: Rothämel
authors.forename: Adam
authors.initials: A
authors.lastname: Grundhoff
authors.forename: Paul
authors.initials: P
authors.lastname: Kellam
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Schulz
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000378:metabolism; D001402:B-Lymphocytes / Q000821:virology*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D019288:Herpesvirus 8, Human / Q000502:physiology*; D006801:Humans; D015151:Immunoblotting; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D000071701:Regulatory Factor X Transcription Factors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D014157:Transcription Factors / Q000378:metabolism; D014709:Vero Cells; D014775:Virus Activation / Q000502:physiology*; D017735:Virus Latency / Q000502:physiology*; D000071717:X-Box Binding Protein 1
chemical_list: D000888:Antibodies, Anti-Idiotypic; D017931:DNA Primers; D004268:DNA-Binding Proteins; D011947:Receptors, Antigen, B-Cell; D000071701:Regulatory Factor X Transcription Factors; D013778:Tetrazolium Salts; D013844:Thiazoles; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; C044203:anti-IgM; D058539:Phosphatidylinositol 3-Kinase; C022616:thiazolyl blue