文章：

卡波西肉瘤及其相关疱疹病毒

Kaposi's sarcoma and its associated herpesvirus

原文发布日期：2010-09-24

DOI: 10.1038/nrc2888

类型: Review Article

开放获取: 否

要点：

1. Kaposi's sarcoma herpesvirus (KSHV; also known as human herpesvirus 8 (HHV8)) is the causative agent of Kaposi's sarcoma (KS) and certain lymphoproliferations, and its seroepidemiology correlates with the global incidence of KS.
2. KS is the most common neoplasm in untreated HIV-infected individuals, and also occurs in other states of immunosuppression, including after an organ transplant.
3. KSHV is transmitted through saliva and replicates in oropharyngeal cells.
4. Unlike most cancer cells, KS tumour cells are not fully transformed, do not show autonomous growth, and remain dependent on exogenous cytokines for in vitro growth.
5. KS starts as a proliferation of endothelial-type cells, with an early onset inflammatory and abnormal leaky blood vessel expansion.
6. KSHV is present in the vast majority of KS tumour cells (that is, spindle cells), expressing the latent viral proteins, including viral cyclin, viral FLICE inhibitory protein, latency-associated nuclear antigen (LANA) and a group of viral microRNAs.
7. A proportion of cells in KS lesions seem to undergo lytic replication, expressing lytic viral proteins including K1, viral interleukin-6, viral BCL-2, viral G protein-coupled receptor, K15 and viral chemokines.
8. KSHV latent genes drive cell proliferation and prevent apoptosis; whereas KSHV lytic genes could further contribute to KS tumorigenesis by triggering host signalling cascades that lead to cytokine and growth factor secretion.
9. Biological insights into KSHV oncogenesis are leading to promising rational therapeutic approaches.

要点翻译：

1. 卡波西肉瘤相关疱疹病毒（KSHV；亦称为人类疱疹病毒8型（HHV8））是卡波西肉瘤（KS）及某些淋巴细胞增殖性疾病的致病因子，其血清流行病学特征与KS的全球发病率具有相关性。
2. KS是未经治疗的HIV感染者中最常见的肿瘤，同时也见于其他免疫抑制状态（包括器官移植后）。
3. KSHV通过唾液传播，并在口咽细胞中复制。
4. 与大多数癌细胞不同，KS肿瘤细胞并非完全转化，不呈现自主生长特性，其体外生长仍依赖外源性细胞因子。
5. KS起始于内皮样细胞的增殖，早期表现为炎症反应及异常渗漏性血管扩张。
6. 绝大多数KS肿瘤细胞（即梭形细胞）中存在KSHV，这些细胞表达潜伏期病毒蛋白，包括病毒周期蛋白、病毒FLICE抑制蛋白、潜伏相关核抗原（LANA）以及一组病毒微小RNA。
7. KS病灶中部分细胞似乎会发生裂解性复制，表达包括K1、病毒白细胞介素-6、病毒BCL-2、病毒G蛋白偶联受体、K15及病毒趋化因子在内的裂解期病毒蛋白。
8. KSHV潜伏期基因驱动细胞增殖并阻止细胞凋亡；而KSHV裂解期基因可通过触发导致细胞因子和生长因子分泌的宿主信号级联反应，进一步促进KS肿瘤发生。
9. 对KSHV致癌机制的生物学认知正在引领具有前景的靶向治疗策略发展。

英文摘要：

Kaposi's sarcoma (KS) is the most common cancer in HIV-infected untreated individuals. Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 (HHV8)) is the infectious cause of this neoplasm. In this Review we describe the epidemiology of KS and KSHV, and the insights into the remarkable mechanisms through which KSHV can induce KS that have been gained in the past 16 years. KSHV latent transcripts, such as latency-associated nuclear antigen (LANA), viral cyclin, viral FLIP and viral-encoded microRNAs, drive cell proliferation and prevent apoptosis, whereas KSHV lytic proteins, such as viral G protein-coupled receptor, K1 and virally encoded cytokines (viral interleukin-6 and viral chemokines) further contribute to the unique angioproliferative and inflammatory KS lesions through a mechanism called paracrine neoplasia.

摘要翻译： 

卡波西肉瘤（KS）是未经治疗的HIV感染者中最常见的癌症。卡波西肉瘤相关疱疹病毒（KSHV，又称人类疱疹病毒8型（HHV8））是这种肿瘤的感染原因。在本综述中，我们描述了KS和KSHV的流行病学，以及过去16年中获得的关于KSHV如何诱导KS的显著机制的见解。KSHV潜伏转录物，如潜伏相关核抗原（LANA）、病毒周期蛋白、病毒FLIP和病毒编码的微小RNA，驱动细胞增殖并防止细胞凋亡，而KSHV裂解蛋白，如病毒G蛋白偶联受体、K1和病毒编码的细胞因子（病毒白细胞介素-6和病毒趋化因子），通过一种称为旁分泌肿瘤形成的机制进一步促进独特的血管增殖性和炎症性KS病变。

原文链接：

Kaposi's sarcoma and its associated herpesvirus