AN INTEGRAL MEMBRANE-PROTEIN (LMP2) BLOCKS REACTIVATION OF EPSTEIN-BARR-VIRUS FROM LATENCY FOLLOWING SURFACE-IMMUNOGLOBULIN CROSS-LINKING

被引:212
作者
MILLER, CL
LEE, JH
KIEFF, E
LONGNECKER, R
机构
[1] HARVARD UNIV,SCH MED,DEPT MED,BOSTON,MA 02115
[2] HARVARD UNIV,SCH MED,DEPT MICROBIOL & MOLEC GENET,BOSTON,MA 02115
关键词
D O I
10.1073/pnas.91.2.772
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The role of latent membrane protein 2 (LMP2) in Epstein-Barr virus (EBV) infection was evaluated by using latently infected primary B lymphocytes that had been growth transformed by wild-type or specifically mutated EBV recombinants. LMP2 null mutant recombinant EBV-infected cells were similar to normal B lymphocytes in their rapid increase in intracellular free calcium after surface immunoglobulin crosslinking. These cells also became more permissive for lytic EBV replication. In sharp contrast, wild-type control infected cells had little or no increase in intracellular free calcium or in permissivity For EBV replication. The block to surface immunoglobulin crosslinking induced permissivity in cells expressing wild-type LMP2 could be bypassed by raising intracellular free calcium levels with an ionophore and by activating protein kinase C with phorbol 12-myristate 13-acetate. LMP2A, not LMP2B, mediates this effect on calcium mobilization. Genetic and biochemical data are consistent with these effects being due to the interaction of the LMP2A N-terminal cytoplasmic domain with B lymphocyte src family tyrosine kinases.
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页码:772 / 776
页数:5
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