HHV-8 AND KAPOSI'S SARCOMA

卡波西肉瘤[KS]是一种肿瘤样病变， 环境，包括某些种族背景的老年男性，肾 移植患者，非洲部分地区的居民，以及HIV-1感染者 人在后一种情况下，它遵循的是一条更为激进的路线 比没有HIV-1的情况下要多。最近发现的人类疱疹病毒， 称为KS疱疹病毒[KSHV]或人疱疹病毒8型[HHV 8]， 普遍存在于所有形式的KS，这表明它是一个必要的病因 KS的因素。目前尚不清楚KS是肿瘤还是仅仅是一种肿瘤。 增生HS病变具有复杂的细胞组成，包括 巨噬细胞、淋巴细胞和梭形细胞， 被认为是异常细胞梭形细胞的起源尚不清楚， 它们可能来自不止一个谱系。几乎所有主轴 然而，细胞含有HHV-8，如原位杂交所示，进一步 提示HHV-8在KS中起作用。KS病变富含 炎症细胞因子，KS的发展似乎部分是 由细胞因子和生长因子的异常表达驱动。我们和 其他研究表明，HHV-8编码结构和功能同源物， 几种细胞因子、趋化因子和趋化因子受体基因。是 本项目的目的是探索病毒和 细胞因子和趋化因子对病毒复制和KS 发病机制具体而言，IL-1 β、IL-6、TNF-α、IFN-γ γ和抑瘤素M对HHV-8复制和基因表达的影响将被 测定在观察到这种效应的情况下， 将确定宿主细胞因子的抑制。表达 KS中的病毒细胞因子/趋化因子基因[vIL-6、vMIP-1A和-B和ORF 74] 将通过RT-PCR、免疫组织化学和血清学进行表征。 这些病毒基因的功能方面将通过在 体外和转基因小鼠中。这将包括他们对 KS病变在小鼠模型系统中的生长。这些研究的结果 将提供关于宿主和病毒作用的重要信息， 细胞因子和趋化因子对HHV-8表达和KS发病机制的影响。

Kaposi's sarcoma [KS] is a tumor-like lesion that occurs in a variety of settings, including in elderly men of certain ethnic backgrounds, renal transplant patients, residents of parts of Africa, and HIV-1 infected people. In the latter setting, it follows a far more aggressive course than in the absence of HIV-1. A recently identified human herpesvirus, called KS herpesvirus [KSHV] or human herpesvirus type 8 [HHV8], is prevalent in all forms of KS, suggesting that it is a necessary etiologic factor for KS. It is not clear whether KS is a tumor or merely a hyperplasia. HS lesions have a complex cellular makeup that includes macrophages, lymphocytes, and cells with a spindle morphology, which are thought to be the abnormal cell. The origin of spindle cells is not clear, and they may originate from more than one linage. Virtually all spindle cells, however, contain HHV-8, as shown by in situ hybridization, further suggesting that HHV-8 plays a role in KS. KS lesions are rich in inflammatory cytokines, and the development of KS appears in part to be drive by abnormal expression of cytokines and growth factors. We and others have shown that HHV-8 codes for structural and functional homologs of several cytokine, chemokine and chemokine receptor genes. It is the purpose of this project to explore the relationships of the viral and cellular cytokines and chemokines to virus replication and KS pathogenesis. Specifically, the effects of IL-1beta, IL-6, TNF-alpha, IFN- gamma and oncostatin M on HHV-8 replication and gene expression will be determined. Where such effects are observed, the mechanisms of activation of repression by the host cytokines will be determined. Expression of viral cytokine/chemokine genes [vIL-6, vMIP-1A and -B and ORF74] in KS will be characterized by RT-PCR, immunohistochemistry and serology. Functional aspects of these viral genes will be analyzed by expression in vitro and in transgenic mice. This will include their influence on the growth of KS lesions in mouse model systems. Results from these studies will provide important information on the roles of host and viral cytokines and chemokines on HHV-8 expression and KS pathogenesis.