Enhanced susceptibility of B lymphoma cells to measles virus by Epstein-Barr virus type III latency that upregulates CD150/signaling lymphocytic activation molecule.
Bottom Line: Among EBV-encoded genes, latent membrane protein 1 was responsible for the CD150 upregulation.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.
Affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.Show MeSH
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Mentions: The cytolytic activity of three MV strains was examined in BLCL, a historical model of EBV-positive DLBCL, including a WT MV and two vaccine strains either non-Edmonston-derived CAM-70 or Edmonston-derived Schwarz. The LD50 at 7 days post-infection by CAM-70, Schwarz, and the WT MV were <0.03, 0.4, and 0.04 in BLCL, respectively. These data suggest that CAM-70 is potent in infecting and killing BLCL cells and, to our surprise, more potent than Schwarz (Fig. 1a). To verify these findings, we examined two representative B lymphoma cell lines showing type III EBV latency, Raji and Jijoye. The LD50 values in Raji were <0.03, >2.0, and 0.6 by CAM-70, Schwarz, and the WT MV, respectively (Fig. 1b). Similarly, in Jijoye, the LD50 values were estimated as <0.03, 0.1, and 0.03 by CAM-70, Schwarz, and the WT MV, respectively (Fig. 1c). We examined P3HR-1, a subclone from Jijoye latently infected with a defective EBV lacking EBNA2 and a part of EBNA-leader protein (LP) genes as yet expressing LMP1 at low levels.(34) The LD50 values of P3HR-1 were <0.03, 0.9, and 0.04 by CAM-70, Schwarz, and the WT MV, respectively, comparable to Jijoye (Fig. 1d). Additionally, Namalwa cells were susceptible only to the CAM-70 strain (Fig. 1e). These data suggest that CAM-70 has a greater potency in killing B lymphoma cells bearing type III EBV latency.
Affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.