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

Cancer Science

Satoshi Takeda²  Daiki Kanbayashi¹  Takako Kurata¹  Hironori Yoshiyama³ 

[1] Department of Infectious Diseases, Virology Division, Osaka Prefectural Institute of Public Health, Osaka, Japan;AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan;Research Center for Infection-associated Cancer, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan

关键词: B‐cell lymphoma;    CD150/signaling lymphocytic activation molecule;    Epstein–Barr virus;    latent membrane protein 1;    measles virus oncolytic virotherapy;   

DOI  :  10.1111/cas.12324

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

CC BY-NC-ND   
© 2013 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

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