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

Takeda S, Kanbayashi D, Kurata T, Yoshiyama H, Komano J - Cancer Sci. (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.

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Related in: MedlinePlus

Upregulation of CD150/signaling lymphocytic activation molecule (SLAM) in B lymphoma cells with type III Epstein–Barr virus (EBV) latency. The flow cytometric profiles of CD46/membrane cofactor protein and CD150/SLAM on various B lymphoma cell lines are shown. The dotted line indicates CD46/membrane cofactor protein, the bold line CD150/SLAM, and the shaded the isotype control. RLU, relative light unit.
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fig03: Upregulation of CD150/signaling lymphocytic activation molecule (SLAM) in B lymphoma cells with type III Epstein–Barr virus (EBV) latency. The flow cytometric profiles of CD46/membrane cofactor protein and CD150/SLAM on various B lymphoma cell lines are shown. The dotted line indicates CD46/membrane cofactor protein, the bold line CD150/SLAM, and the shaded the isotype control. RLU, relative light unit.

Mentions: The cell surface levels of MV receptors determine the cellular susceptibility to MV infection. In lymphoid cells, two MV receptors are expressed, CD46/MCP(10,11) and CD150/SLAM.(35) We investigated whether the cell surface levels of these molecules were upregulated in cells with type III latency compared with those without EBV infection or with type I latency (Fig. 3). All cell lines were positive for CD46. However, CD150 was barely detected in EBV-negative Akata, Daudi, BL-41, and Mutu cells. Type III latency cells showed higher levels of CD150 than type I counterparts in BL41, BJAB, and Mutu cells. The average magnitude of CD150 upregulation by type III latency was 3.8-fold (3.2-, 3.4-, and 4.7-fold in BL41, BJAB, and Mutu cells, respectively). In contrast, a similar effect was not observed in CD46 except that the levels of CD46 was upregulated in type III latency in Mutu cells by 4.6-fold. Such effects were not observed in Akata and Daudi cells, suggesting that the CD150 upregulation was restricted to type III EBV latency. In agreement with our findings, increased levels of CD150 on type III Mutu cells were reported previously.(42) The vaccine strains of MV use both CD46 and CD150 as receptors. However, the WT MV used in this study was CD46-blind. Given that the cytolytic activity of the WT MV was largely paralleled to that of CAM-70, and the increased susceptibility to MV's cytolytic activity was observed only in the cells with type III EBV latency, it was likely the major determinant of MV's enhanced cytolytic activity was the cell surface CD150. Historically, it was emphasized that MV OVT targets the increased levels of CD46 on tumor cells using vaccine strains of MV.(12) However, our data point out that CD150 plays a major role in the killing of B lymphoma cells by MV. It is noted that BJAB cells were unique for their susceptibility to CAM-70 (Fig. 2b) due to the expression of CD150 at low levels in the absence of EBV latent infection, unlike other B lymphoma cell lines (Fig. 3).


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

Takeda S, Kanbayashi D, Kurata T, Yoshiyama H, Komano J - Cancer Sci. (2014)

Upregulation of CD150/signaling lymphocytic activation molecule (SLAM) in B lymphoma cells with type III Epstein–Barr virus (EBV) latency. The flow cytometric profiles of CD46/membrane cofactor protein and CD150/SLAM on various B lymphoma cell lines are shown. The dotted line indicates CD46/membrane cofactor protein, the bold line CD150/SLAM, and the shaded the isotype control. RLU, relative light unit.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4317819&req=5

fig03: Upregulation of CD150/signaling lymphocytic activation molecule (SLAM) in B lymphoma cells with type III Epstein–Barr virus (EBV) latency. The flow cytometric profiles of CD46/membrane cofactor protein and CD150/SLAM on various B lymphoma cell lines are shown. The dotted line indicates CD46/membrane cofactor protein, the bold line CD150/SLAM, and the shaded the isotype control. RLU, relative light unit.
Mentions: The cell surface levels of MV receptors determine the cellular susceptibility to MV infection. In lymphoid cells, two MV receptors are expressed, CD46/MCP(10,11) and CD150/SLAM.(35) We investigated whether the cell surface levels of these molecules were upregulated in cells with type III latency compared with those without EBV infection or with type I latency (Fig. 3). All cell lines were positive for CD46. However, CD150 was barely detected in EBV-negative Akata, Daudi, BL-41, and Mutu cells. Type III latency cells showed higher levels of CD150 than type I counterparts in BL41, BJAB, and Mutu cells. The average magnitude of CD150 upregulation by type III latency was 3.8-fold (3.2-, 3.4-, and 4.7-fold in BL41, BJAB, and Mutu cells, respectively). In contrast, a similar effect was not observed in CD46 except that the levels of CD46 was upregulated in type III latency in Mutu cells by 4.6-fold. Such effects were not observed in Akata and Daudi cells, suggesting that the CD150 upregulation was restricted to type III EBV latency. In agreement with our findings, increased levels of CD150 on type III Mutu cells were reported previously.(42) The vaccine strains of MV use both CD46 and CD150 as receptors. However, the WT MV used in this study was CD46-blind. Given that the cytolytic activity of the WT MV was largely paralleled to that of CAM-70, and the increased susceptibility to MV's cytolytic activity was observed only in the cells with type III EBV latency, it was likely the major determinant of MV's enhanced cytolytic activity was the cell surface CD150. Historically, it was emphasized that MV OVT targets the increased levels of CD46 on tumor cells using vaccine strains of MV.(12) However, our data point out that CD150 plays a major role in the killing of B lymphoma cells by MV. It is noted that BJAB cells were unique for their susceptibility to CAM-70 (Fig. 2b) due to the expression of CD150 at low levels in the absence of EBV latent infection, unlike other B lymphoma cell lines (Fig. 3).

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.

View Article: PubMed Central - PubMed

Affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.

Show MeSH
Related in: MedlinePlus