Control of Epstein-Barr virus reactivation by activated CD40 and viral latent membrane protein 1
Control of Epstein-Barr virus reactivation by activated CD40 and viral latent membrane protein 1
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DOI：
10.1073/pnas.221439999
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发表时间：
2002-01-08
影响因子：
11.1
通讯作者：
Bornkamm, GW
中科院分区：
文献类型：
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作者：
Adler, B;Schaadt, E;Bornkamm, GW
在人类中，EB 病毒 (EBV) 在外周静息 B 淋巴细胞中建立持续的潜伏感染。病毒的重新激活受到严格限制。在健康人中，感染通常是良性的，而免疫功能低下的患者患 EBV 相关恶性肿瘤的风险增加，同时病毒复制和病毒感染细胞数量增加。为了寻找调节病毒再激活的病毒和宿主因子，我们使用了条件性 EBV 永生化 B 细胞。我们发现 CD40-CD40 配体相互作用和激活的 CD40 的病毒模拟物、EBV 潜伏膜蛋白 1. 抑制病毒重新激活。两者都抑制抗 IgM 或佛波酯诱导的病毒立即早期蛋白 BZLF1 的转录，该蛋白控制进入病毒裂解周期。潜伏膜蛋白 1 和 CD40 有助于调节潜伏期，这一发现可能对正常人和免疫功能低下个体的 EBV 与其宿主之间的平衡具有重要意义。
In humans, Epstein-Barr virus (EBV) establishes a persistent latent infection in peripheral resting B lymphocytes. Virus reactivation is highly restricted. Whereas in healthy humans the infection usually is benign, immunocompromised patients show an increased risk for EBV-associated malignancies, accompanied by an increase in virus replication and in the number of virus-infected cells. To search for viral and host factors regulating virus reactivation, we used conditionally EBV-immortalized B cells. We found that CD40-CD40 ligand interaction and the viral mimic of activated CD40, EBV latent membrane protein 1. suppress virus reactivation. Both inhibit anti-IgM or phorbolester-induced transcription of the viral immediate early protein BZLF1, which controls entry into the viral lytic cycle. The finding that latent membrane protein 1 and CD40 contribute to the regulation of latency may have important implications for the balance between EBV and its host in normal as well as in immunocompromised individuals.