卡波氏肉瘤病毒和巴尔通体介导血管生成的机制差异及相关性研究

Both Kaposi’s sarcoma-associated herpesvirus (KSHV) and Bartonella has been documented to infect human endothelial cell and cause two human malignancies: Kaposi’s sarcoma (KS) and Bacillary angiomatosis (BA), respectively. Due to both KS and BA present highly similarities in clinical symptoms and pathological development, it is difficult to distinguish and leads to numerous misdiagnosis and missed diagnosis in clinic. Moreover, whether these two pathogens co-infect endothelial cells, and the difference and correlation of angiogenesis induced by KSHV and Bartonella through regulating hypoxia signaling pathway, remains largely unknown. In this proposal, we will use our well-established system of human umbilical cord endothelial cells (HUVEC) with KSHV or Bartonella infection in vitro, to explore the difference and correlation of hypoxia signaling-induced angiogenesis regulated by these two pathogens at molecular and cellular levels. In addition, we will investigate the difference and similarity of tumorigenesis induced by these two pathogens in mice tumor model. Our purpose of this study is to provide new targets and fundamentals results for timely diagnosis and treatment of KSHV or Bartonella associated tumor in future.

卡波氏肉瘤病毒（KSHV）与巴尔通体均能感染人血管内皮细胞，并分别引发卡波氏肉瘤(KS)与杆菌性血管瘤(BA)两种人类皮肤恶性肿瘤。由于KS与BA症状与病理变化极为相似，临床上难以区分,且常存在误诊漏诊等现象。此外，临床上KSHV与巴尔通体是否共感染导致并发症？二者引发KS与BA血管增生的机制的异同等问题目前尚未完全清楚。本项目将在前期工作的基础上以人脐带血内皮细胞为研究对象，利用已建立的KSHV和巴尔通体体外感染细胞模型，在分子和细胞水平上，探讨二者体外共感染和诱发缺氧信号促血管生成途径的机制差异和相关性；同时结合小鼠体内肿瘤模型实验明确二者致瘤作用的异同，以期为临床上KSHV与巴尔通体相关肿瘤的及时诊治提供参考和理论依据。

卡波氏肉瘤病毒（KSHV）与巴尔通体均能感染人血管内皮细胞，并分别引发卡波氏肉瘤(KS)与杆菌性血管瘤(BA)两种人类皮肤恶性肿瘤。由于KS与BA症状与病理变化极为相似，临床上难以区分,且常存在误诊漏诊等现象。此外，临床上KSHV与巴尔通体是否共感染导致并发症？二者引发KS与BA血管增生的机制的异同等问题目前尚未完全清楚。本项目将在前期工作的基础上以人脐带血内皮细胞为研究对象，建立了KSHV与巴尔通体分别单独感染及共感染细胞模型，通过光学成像技术及细胞分子生物学技术，发现巴尔通体能够抑制KSHV的感染，通过质谱及western分析发现，共感染后能够引起HIF蛋白上游基因HDAC1和HSP90的高表达。同时建立了体外3D培养类器官的方法，为下一步皮肤类器官的培养及病原显微注射感染皮肤类器官打下了夯实的基础。