卡波氏肉瘤(KS)是艾滋病群体中最主要的恶性肿瘤。艾滋病相关KS病人中，KS往往首先发生在口腔。口腔KS的恶性程度直接反应病人整体KS的进程。但是关于KSHV很多重要的问题还没有解决。 KSHV感染和藏匿在人体什么细胞里？怎样促进KS肿瘤的发生？KS肿瘤细胞从何而来? 我们最近发现人类口腔间充质干细胞（OMSC) 能被KSHV高效感染，并促进其分化，使之具备更强的成脂，成骨和成血管特性。这些发现引导我们提出了一系列新的KSHV致癌理论。1）OMSC可能是KSHV初始感染的目标。2）KSHV感染劫持OMSC细胞发生间充质-内皮细胞转化导致卡波氏肉瘤的产生。我们通过本项目1）研究KSHV感染OMSC，建立潜伏感染和促进分化的机制，希望找到KSHV潜伏感染的OMSC是KS纺梭状细胞前体的证据；2）阐明KSHV转化OMSC诱导其癌变的机制；3）寻求阻止KSHV感染和医治KS的新途径和新药物。

Kaposi’s sarcoma (KS) remains the most common malignancy in AIDS patients. In AIDS-KS patients, oral cavity is often the first site or the only site of KS. Oral KS appears to be more aggressive and malignant than those occur on other sites such as the skin. AIDS-KS lessons are characterized by proliferating KSHV-infected spindle cells and intensive angiogenesis and inflammation. The origin of the spindle cells remains elusive. Recently we found that KSHV can efficiently infect oral mesenchymal stem cells (MSCs) and the infection leads to morphological changes and cells becomes spindle-shaped similar to KS cells. Furthermore, infected MSCs exhibit enhanced ability of adipogenesis, osteogenesis and angiogenesis. These discoveries prompted us to propose a hypothesis that oral MSCs are the primary cells of KSHV infection and the infected MSCs can undergo mesenchymal-to-endothelial transition (MET) and therefore be transformed to KS malignant cells. In the proposed project, we will examine and prove this hypothesis by (1) characterizing oral MSCs infected by KSHV for their stem cell property, differentiation ability and tumor transformation potential; (2) elucidating the process and underlying mechanism of MET in infected oral MSCs. In addition, efforts will be made to identify small molecule compounds that inhibit KSHV infection of oral MSCs and block tumorigenesis of infected MSCs, exploring the potentials of the compounds to be used as new therapeutic strategies and new drugs to treat KS and other KSHV-associated malignancies.