Enhanced susceptibility of B lymphoma cells to measles virus by Epstein-Barr virus type III latency that upregulates CD150/signaling lymphocytic activation molecule

摘要

Measles virus (MV) is one of the candidates for the application of oncolytic virotherapy (OVT). Although an advanced clinical study has been reported on a T-cell lymphoma, the potential of MV OVT against B-cell lymphomas remains to be clarified. We found that an EBV-transformed B lymphoblastoid cell line, a model for diffuse large B-cell lymphoma, and EBV-positive Burkitt's lymphoma cells bearing type III latency were highly susceptible to the cytolysis induced by an MV vaccine strain CAM-70. As analyzed by EBV-positive and -negative counterparts of the same cytogenetic background, type III EBV latency, not type I, was shown to augment the susceptibility of B lymphoma cells to MV-induced cytolysis. Cell surface levels of CD150/signaling lymphocytic activation molecule, a receptor of MV, were upregulated in B lymphoma cell lines with type III EBV latency by 3.8-fold, on average. The cytolytic activity of CD150-tropic WT MV was akin to that of CD46- and CD150-tropic CAM-70, suggesting that CD150 is critical for the susceptibility to MV-induced cytolysis. Among EBV-encoded genes, latent membrane protein 1 was responsible for the CD150 upregulation. It was notable that the majority of B lymphoma cell lines of type III EBV latency showed higher susceptibility to the non-Edmonston-derived CAM-70 than to the Edmonston-derived Schwarz strain. This is the first report indicating the potential of non-Edmonston MV strain for the application of OVT. Furthermore, a cellular regulator of MV replication was implicated that functions in a vaccine strain-specific fashion. Altogether, the MV OVT should serve as an alternative therapy against EBV-positive diffuse large B-cell lymphoma with type III EBV latency.