Corrigendum to “Induction of hyaluronan production by oncogenic KSHV and the contribution to viral pathogenesis in AIDS patients” [Cancer Lett. 2015 Jul 1;362(2):158–66]
Corrigendum to “Induction of hyaluronan production by oncogenic KSHV and the contribution to viral pathogenesis in AIDS patients” [Cancer Lett. 2015 Jul 1;362(2):158–66]
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DOI：
10.1016/j.canlet.2015.07.033
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发表时间：
2015-12
期刊：
影响因子：
9.7
通讯作者：
L. Dai;Yihan Chen;Karlie Bonstaff;Lisa Doyle;B. Toole;D. Whitby;C. Parsons;Zhiqiang Qin
中科院分区：
文献类型：
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作者：
L. Dai;Yihan Chen;Karlie Bonstaff;Lisa Doyle;B. Toole;D. Whitby;C. Parsons;Zhiqiang Qin
Kaposi肉瘤相关疱疹病毒(KSHV)是Kaposi肉瘤(KS)和原发性渗出性淋巴瘤(PEL)的病原体，这两种肿瘤主要发生于免疫功能低下的患者，尤其是艾滋病患者，目前仍缺乏有效的治疗方法。透明质酸(HA)是一种大的葡萄糖醛酸，已被发现与癌细胞的多种功能密切相关，尽管它在病毒致癌中的作用仍很不清楚。在这里，我们提供了新感染KSHVde通过上调HA合成酶基因1(Has1)和多功能糖蛋白CD147诱导原代内皮细胞产生HA的首次证据。进一步的数据表明，KSHV诱导的HA产生需要病毒潜伏蛋白、LANA(特别是功能结构域A)和MAPK/ERK信号活性。在功能上，HA的产生是KSHV/LANA诱导的原代内皮细胞侵袭所必需的，这是KS发生的标志特征。对于临床相关性，我们的数据表明，KSHV+组的血浆中HA和HAS1活性水平高于队列HIV感染患者的KSHV−组。总之，我们的发现对致癌病毒激活HA产生的机制及其在病毒相关恶性肿瘤发病机制中的作用提供了创新性的见解，这可能有助于通过靶向HA及其相关信号来开发新的治疗策略。
Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent for Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL), malignancies arising primarily in immunocompromised patients particularly AIDS-patients, which still lack effective therapy. Hyaluronan (HA) is a large glucuronic acid and has been found closely related to multiple functions in cancer cells, although its role in viral oncogenesis remains largely unknown. Here we provide first evidence that KSHVde novoinfection induces HA production from primary endothelial cells through upregulation of HA synthase gene 1 (Has1) and a multifunctional glycoprotein, CD147. Further data demonstrate that KSHV-induced HA production requires viral latent protein, LANA (in particular functional domain A) and MAPK/ERK signaling activities. In functions, HA production is necessary for KSHV/LANA-induced primary endothelial cell invasion, a hallmark feature for KS development. For clinical relevance, our data indicate that the KSHV+ group has higher levels of HA and Has1 activities in its plasma than the KSHV− group of cohort HIV-infected patients. Together, our findings provide innovative insights into the mechanisms of oncogenic virus activation of HA production and its role in virus-associated malignancy pathogenesis, which may help to develop novel therapeutic strategies by targeting HA and related signaling.