A membrane-located glycosphingolipid of monocyte/granulocyte lineage cells induces growth arrest and triggers the lytic viral cycle in Epstein-Barr virus genome-positive Burkitt lymphoma lines.
Gangliosides are known to influence cell growth and differentiation. The neolacto series ganglioside IV3NeuAc-nLc4 (2-->3-sialosylparagloboside) is present in members of the monocyte/granulocyte lineage, but is not found in cells that belong to the lymphocyte lineage. In this study we demonstrated that IV3NeuAc-nLc4 inhibits the proliferation of Epstein-Barr virus (EBV) genome-positive Burkitt lymphoma cells of the lines Raji and P3HR-1K. IV3NeuAc-nLc4-induced growth inhibition is associated with an increase in G0/G1 phase cells and a reduced expression of CD21 and HLA-DR antigens on Raji cells. These data suggest that IV3NeuAc-nLc4 may affect differentiation of lymphoma cells. Additionally, the increased expression of viral mRNA species which are characteristic for the lytic viral cycle in the non-producer line Raji and the enhanced release of virions from the producer line P3HR-1K demonstrate that IV3NeuAc-nLc4 activates the replication of EBV. Growth inhibition and termination of the viral latency suggest that IV3NeuAc-nLc4 present in monocyte/granulocyte lineage cells may be an effector of the natural defense against EBV persistency and transformation.
Schaade
L
L
Department of Medical Microbiology, University Hospital, RWTH Aachen, Germany. lschaade@alpha.imib.rwth-aachen.de
Kleines
M
M
Walter
R
R
Thomssen
R
R
Ritter
K
K
D017209:Apoptosis; D001402:B-Lymphocytes / Q000502:physiology* / Q000821:virology; D002051:Burkitt Lymphoma / Q000473:pathology* / Q000821:virology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D019070:Cell Lineage; D002462:Cell Membrane / Q000737:chemistry; D005434:Flow Cytometry; D005915:Globosides / Q000494:pharmacology*; D006098:Granulocytes / Q000737:chemistry; D004854:Herpesvirus 4, Human / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D009000:Monocytes / Q000737:chemistry; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism; D017735:Virus Latency / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
D005915:Globosides; D012333:RNA, Messenger; D014764:Viral Proteins; C014812:sialosylparagloboside