Rescue of the Epstein-Barr virus BZLF1 mutant, Z(S186A), early gene activation defect by the BRLF1 gene product
Rescue of the Epstein-Barr virus BZLF1 mutant, Z(S186A), early gene activation defect by the BRLF1 gene product
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DOI：
10.1006/viro.1998.9396
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发表时间：
1998-11-10
期刊：
影响因子：
3.7
通讯作者：
Kenney, SC
中科院分区：
文献类型：
--
作者：
Adamson, AL;Kenney, SC
EB病毒(EBV)即刻早期蛋白BZLF1(Z)的表达足以破坏病毒潜伏期。Z通过与上游Z反应元件(ZRE)结合，转录激活EBV早期基因。最近，Z残基186的丝氨酸到丙氨酸突变(在基本DNA结合域内)被证明抑制了Z在潜伏感染细胞中诱导裂解感染的能力，尽管Z(S186A)突变体仍然可以结合几个已知的ZRE并在瞬时报告基因分析中激活早期EBV启动子(BMRF1)(Francis，A.L.，Gradoville，L.，and Miller，G.(1997))。J.维罗尔。71、3054-3061)。我们现在发现，在即刻早期BRLF1启动子中与ZRE元件结合的能力的特定缺陷可能是Z(S186A)无法激活BRLF1表达的原因。此外，我们还证明了Z(S186A)诱导BMRF1和BH RFI基因早期表达的能力可以通过与BRLF1表达载体的共转染来挽救。然而，Z(S186A)/BRLF1(R)组合不能诱导完全的裂解复制，这表明Z(S186A)可能也缺乏复制特异性功能。这些结果表明，在完整的病毒基因组的背景下，Z和R的表达都是激活潜伏感染细胞中早期基因转录所必需的，(C)1998年学术出版社。
Expression of the Epstein-Barr virus (EBV) immediate-early protein, BZLF1 (Z), is sufficient to disrupt viral latency. Z transcriptionally activates the EBV early genes by binding to upstream Z-responsive elements (ZREs). Recently, a serine-to-alanine mutation of Z residue 186 (within the basic DNA binding domain) was shown to inhibit the ability of Z to induce lytic infection in latently infected cells, although the Z(S186A) mutant could still bind several known ZREs and activated an early EBV promoter (BMRF1) in transient reporter gene assays (Francis, A. L., Gradoville, L., and Miller, G. (1997). J. Virol. 71, 3054-3061). We now show that a specific deficiency in the ability to bind to ZRE elements in the immediate-early BRLF1 promoter may account for the inability of Z(S186A) to activate BRLF1 expression. Furthermore, we demonstrate that the ability of Z(S186A) to induce early BMRF1 and BH RFI gene expression is rescued by cotransfection with a BRLF1 expression vector. However, the Z(S186A)/BRLF1 (R) combination cannot induce full lytic replication, suggesting that Z(S186A) may also be deficient in a replication-specific function. These results suggest that in the context of the intact viral genome, both Z and R expression are required for activation of early gene transcription in latently infected cells, (C) 1998 Academic Press.