Hypoxia induces lytic replication of Kaposi sarcoma-associated herpesvirus
Hypoxia induces lytic replication of Kaposi sarcoma-associated herpesvirus
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DOI：
10.1182/blood.v97.10.3244
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发表时间：
2001-05-15
期刊：
影响因子：
20.3
通讯作者：
Yarchoan, R
中科院分区：
文献类型：
--
作者：
Davis, DA;Rinderknecht, AS;Yarchoan, R
大量证据表明，卡波西肉瘤相关疱疹病毒(KSHV)在所有类型的卡波西肉瘤(KS)的发病机制中起重要作用。人们已经注意到，KS通常发生在组织氧合不良的部位，如足部。在此基础上，通过研究两个潜伏感染KSHV的原发渗出性淋巴瘤B细胞系BC-3和BCBL-1，探讨了低氧在KSHV复制重新激活中的潜在作用。急性和慢性缺氧(11%O-2)诱导KSHV裂解复制，表现为细胞内裂解蛋白表达增加，免疫印迹检测到细胞上清液中的病毒。此外，低氧还使分泌的病毒白介素6水平增加。此外，低氧增强了病毒诱导剂12-O-十四烷基佛波醇-13-乙酸酯启动的裂解复制。去铁胺和氯化钴，两种增加细胞内缺氧诱导因子1水平的化合物，也能够诱导KSHV裂解复制。这些研究表明，低氧是KSHV复制的诱导者。这一过程可能在KS的发病机制中起重要作用。(血。2001年；97：3244-3250)(C)2001，由美国血液病学会主办。
There is substantial evidence that Kaposi sarcoma-associated herpesvirus (KSHV) plays an important role in the pathogenesis of all forms of Kaposi sarcoma (KS). It has been noted that KS commonly occurs in locations, such as the feet, where tissue may be poorly oxygenated. On the basis of this observation, the potential role of hypoxia in the reactivation of KSHV replication was explored by studying 2 KSHV-infected primary effusion lymphoma B-cell lines (BC-3 and BCBL-1) latently infected with KSHV. Acute and chronic exposure of these cells to hypoxia (11% O-2) induced KSHV lytic replication, as indicated by an increase in intracellular lytic protein expression and detection of virus in cell supernatants by Western immunoblotting. In addition, hypoxia increased the levels of secreted viral interleukin-6. Moreover, hypoxia enhanced the lytic replication initiated by the viral inducer 12-O-tetradecanoylphorbol-13-acetate. Desferoxamine and cobalt chloride, 2 compounds that increase the intracellular levels of hypoxia-inducible factor 1, were also able to induce KSHV lytic replication. These studies suggest that hypoxia is an inducer of KSHV replication. This process may play an important role in the pathogenesis of KS. (Blood. 2001;97:3244-3250) (C) 2001 by The American Society of Hematology.