X-Box Binding Protein 1 Contributes to Induction of the Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycle under Hypoxic Conditions
X-Box Binding Protein 1 Contributes to Induction of the Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycle under Hypoxic Conditions
复制标题
DOI：
10.1128/jvi.00076-09
复制
发表时间：
2009-07-15
影响因子：
5.4
通讯作者：
Kellam, Paul
中科院分区：
文献类型：
--
作者：
Dalton-Griffin, Lucy;Wilson, Sam J.;Kellam, Paul
卡波西肉瘤相关疱疹病毒（KSHV）与其他疱疹病毒一样，其生命周期有两个阶段：潜伏期和裂解复制。KSHV是卡波西肉瘤（一种内皮源性肿瘤）发展所必需的，并与B细胞肿瘤原发性渗出性淋巴瘤（PEL）和多中心Castleman病的浆细胞瘤变体相关，所有这些疾病的特征都是主要的潜伏性KSHV感染。最近，我们和其他人已经表明，激活形式的转录因子X-box结合蛋白1（XBP-1）是一个生理触发KSHV裂解再激活的PEL。在这里，我们表明，XBP-1 s反式激活ORF 50/RTA启动子，通过ACGT核心含有XBP-1的反应元件，一个元素以前确定为弱活性缺氧反应元件（HRE）。低氧诱导KSHV裂解周期，并且响应低氧诱导因子1 α的活性HRE存在于ORF 50/RTA启动子中。缺氧也诱导活跃的XBP-1，在这里，我们表明，这两个转录因子有助于诱导RTA的表达，导致在缺氧条件下产生感染性KSHV。
Kaposi's sarcoma-associated herpesvirus (KSHV), like other herpesviruses, has two stages to its life cycle: latency and lytic replication. KSHV is required for development of Kaposi's sarcoma, a tumor of endothelial origin, and is associated with the B-cell tumor primary effusion lymphoma (PEL) and the plasmablastic variant of multicentric Castleman's disease, all of which are characterized by predominantly latent KSHV infection. Recently, we and others have shown that the activated form of transcription factor X-box binding protein 1 (XBP-1) is a physiological trigger of KSHV lytic reactivation in PEL. Here, we show that XBP-1s transactivates the ORF50/RTA promoter though an ACGT core containing the XBP-1 response element, an element previously identified as a weakly active hypoxia response element (HRE). Hypoxia induces the KSHV lytic cycle, and active HREs that respond to hypoxia-inducible factor 1 alpha are present in the ORF50/RTA promoter. Hypoxia also induces active XBP-1s, and here, we show that both transcription factors contribute to the induction of RTA expression, leading to the production of infectious KSHV under hypoxic conditions.