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Target and effector cell fusion accounts for B lymphocyte-mediated lysis of mouse hepatitis virus-infected cells
M Wysocka1, R Korngold, J Yewdell
1Wistar Institute, Philadelphia, Pennsylvania 19104.
In confirmation of previous reports, we observed lysis of mouse hepatitis virus (MHV)-infected target cells in the presence of spleen and lymph node cells from nonimmunized mice possessing a B cell surface phenotype (IgM+, IgG+, J11d+, Ia+, Fc+, Thy1-, MAC-1- and asialo-GM1-). Lysis was inhibited by MHV-specific antisera. The presence of immunoglobulin at the surface of B cells is not required for cytolysis since MHV-infected target cells are lysed in the presence of the B cell hybridoma Sp2/0, which fails to synthesize immunoglobulin. Using 51Cr-labelled Sp2/0 cells, both target and effector cells were shown to undergo cytolysis. Direct observation of target and effector cells co-incubated after labelling with different fluorescent dyes demonstrated that lysis correlates with the fusion of B cells and MHV-infected cells. These findings are consistent with the idea that the E2 protein of MHV, which is expressed on the infected cell surface and has receptor and membrane-fusion activities at neutral pH, selectively mediates fusion with cells of B lymphocyte lineage. This may represent a general mechanism by which enveloped viruses with fusion proteins that function at neutral pH can interfere with the function of subsets of immune cells.
In confirmation of previous reports, we observed lysis of mouse hepatitis virus (MHV)-infected target cells in the presence of spleen and lymph node cells from nonimmunized mice possessing a B cell surface phenotype (IgM+, IgG+, J11d+, Ia+, Fc+, Thy1-, MAC-1- and asialo-GM1-). Lysis was inhibited by MHV-specific antisera. The presence of immunoglobulin at the surface of B cells is not required for cytolysis since MHV-infected target cells are lysed in the presence of the B cell hybridoma Sp2/0, which fails to synthesize immunoglobulin. Using 51Cr-labelled Sp2/0 cells, both target and effector cells were shown to undergo cytolysis. Direct observation of target and effector cells co-incubated after labelling with different fluorescent dyes demonstrated that lysis correlates with the fusion of B cells and MHV-infected cells. These findings are consistent with the idea that the E2 protein of MHV, which is expressed on the infected cell surface and has receptor and membrane-fusion activities at neutral pH, selectively mediates fusion with cells of B lymphocyte lineage. This may represent a general mechanism by which enveloped viruses with fusion proteins that function at neutral pH can interfere with the function of subsets of immune cells.
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