Terminal differentiation into plasma cells initiates the replicative cycle of Epstein-Barr virus in vivo
Terminal differentiation into plasma cells initiates the replicative cycle of Epstein-Barr virus in vivo
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DOI：
10.1128/jvi.79.2.1296-1307.2005
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发表时间：
2005-01-01
影响因子：
5.4
通讯作者：
Thorley-Lawson, DA
中科院分区：
文献类型：
--
作者：
Laichalk, LL;Thorley-Lawson, DA
本文证明在健康携带者扁桃体中启动EB病毒复制的细胞是浆细胞(CD38(Hi)，CD10(-)，CD19(+)，CD20(Lo)，表面免疫球蛋白阴性，胞浆免疫球蛋白阳性)。我们进一步得出结论，启动病毒复制的是分化成浆细胞，而不是诱导分化的信号。体外研究证实了这一点，研究表明，启动病毒复制的基因BZLF1的启动子只有在记忆细胞分化为浆细胞后才变得活跃，在浆细胞系中也是活跃的。这与BZLF1在体外的重新激活不同，BZLF1在体外发生急性激活，与细胞凋亡有关，而与分化无关。我们认为分化和急性应激是体内EBV重新激活的两种不同途径。复制病毒的细胞比例随着细胞在裂解周期中的进展而减少，因此只有一小部分细胞实际上释放了传染性病毒。这可能反映了细胞免疫反应对细胞的流产复制或消除。与后一结论一致，这些细胞没有下调主要组织相容性复合体I类分子，这表明这不是EBV使用的免疫逃避策略，这些细胞仍然容易受到细胞毒性T淋巴细胞的攻击。
In this paper we demonstrate that the cells which initiate replication of Epstein-Barr virus (EBV) in the tonsils of healthy carriers are plasma cells (CD38(hi), CD10(-), CD19(+), CD20(lo), surface immunoglobulin negative, and cytoplasmic immunoglobulin positive). We further conclude that differentiation into plasma cells, and not the signals that induce differentiation, initiates viral replication. This was confirmed by in vitro studies showing that the promoter for BZLF1, the gene that begins viral replication, becomes active only after memory cells differentiate into plasma cells and is also active in plasma cell lines. This differs from the reactivation of BZLF1 in vitro, which occurs acutely and is associated with apoptosis and not with differentiation. We suggest that differentiation and acute stress represent two distinct pathways of EBV reactivation in vivo. The fraction of cells replicating the virus decreases as the cells progress through the lytic cycle such that only a tiny fraction actually release infectious virus. This may reflect abortive replication or elimination of cells by the cellular immune response. Consistent with the later conclusion, the cells did not down regulate major histocompatibility complex class I molecules, suggesting that this is not an immune evasion tactic used by EBV and that the cells remain vulnerable to cytotoxic-T-lymphocyte attack.