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

Abstract

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.