Epstein-Barr virus immediate-early protein BZLF1 inhibits tumor necrosis factor alpha-induced signaling and apoptosis by downregulating tumor necrosis factor receptor 1
Epstein-Barr virus immediate-early protein BZLF1 inhibits tumor necrosis factor alpha-induced signaling and apoptosis by downregulating tumor necrosis factor receptor 1
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DOI：
10.1128/jvi.78.1.544-549.2004
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发表时间：
2004-01-01
影响因子：
5.4
通讯作者：
Kenney, SC
中科院分区：
文献类型：
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作者：
Morrison, TE;Mauser, A;Kenney, SC
肿瘤坏死因子α（TNF-α）是宿主免疫和炎症反应的关键介质，并通过溶细胞和非溶细胞机制抑制疱疹病毒复制。TNF-α作用主要通过主要的TNF-α受体TNF-R1介导，TNF-R1在大多数细胞类型中组成型表达。在这里，我们表明，EB病毒（EBV）的立即早期蛋白BZLF 1阻止TNF-α激活的靶基因和TNF-α诱导的细胞死亡。这些作用是通过下调TNF-R1启动子介导的。此外，我们证明了在EBV裂解性复制周期中TNF-R1的表达下调。因此，EBV已经开发了一种新的机制，用于在裂解再活化或原发感染期间逃避TNF-α抗病毒作用。
Tumor necrosis factor alpha (TNF-alpha) is a key mediator of host immune and inflammatory responses and inhibits herpesvirus replication by cytolytic and noncytolytic mechanisms. TNF-alpha effects are primarily mediated through the major TNF-a receptor, TNF-R1, which is constitutively expressed in most cell types. Here we show that the Epstein-Barr virus (EBV) immediate-early protein BZLF1 prevents TNF-alpha activation of target genes and TNF-alpha-induced cell death. These effects are mediated by down-regulation of the promoter for TNF-R1. Additionally, we demonstrate that expression of TNF-R1 is downregulated during the EBV lytic replication cycle. Thus, EBV has developed a novel mechanism for evading TNF-alpha antiviral effects during lytic reactivation or primary infection.