ENVELOPE GLYCOPROTEINS OF HHV8

卡波西肉瘤（KS）是一种常见的艾滋病定义疾病和流行病学特征表明，艾滋病-KS的病因涉及性传播媒介。 新发现的人类疱疹病毒-8（HHV-8）与非AIDS和AIDS KS的病因密切相关。 新兴的血清学研究表明，HHV-8感染的血清阳性率在以性传播为主的美国普通人群中较低。 我们正在进行的研究表明，HHV-8在免疫监视减少的情况下重新激活可能先于AIDS-KS的发展。 未来对HHV-8感染的有效管理应包括控制措施，如针对HHV-8的主动免疫。 我们的研究表明，HHV-8糖蛋白是人体免疫应答的良好靶点，并表明引发针对HHV-8包膜糖蛋白的免疫应答将提供有效的抗感染控制。 序列数据显示，与其他疱疹病毒一样，HHV-8编码几种糖蛋白。 然而，关于HHV-8糖蛋白的身份，性质和功能的知识是有限的，大多数可用的信息来自我们正在进行的研究。总体目标是定义免疫原性包膜HHV-8糖蛋白，定义它们在HHV-8生物学中的作用，并定义针对它们的免疫应答。 通过用HIV+KS+血清筛选HHV-8 cDNA文库，鉴定了编码糖蛋白gB（ORF 8）的cDNA和来自HHV-8 K8.1基因的cDNA。 K8.1基因编码两种糖蛋白，K8.1A和B，这两种糖蛋白是HHV-8所特有的，并由剪接的转录物产生。 对人血清的研究表明，K8.1 A和B是免疫原性糖蛋白。 我们假设ORF K8.1（A和B）和g B糖蛋白介导重要的生物学功能。我们目前的重点是表征K8.1和gB（ORF 8）糖蛋白。 我们制定了以下主要的具体目标：1. 确定感染细胞和病毒包膜中K8.1（A和B）和g B糖蛋白的存在和性质，并确定其生化和结构特性。 2.确定K8.1（A和B）和gB糖蛋白在HHV-8生物学中的作用。 3. 确定K8.1（A和B）和g B糖蛋白与宿主细胞表面受体的潜在相互作用，并对其进行鉴别。 这些研究具有重要意义，因为对HHV-8 ORF K8.1（A和B）和gB的分子、抗原和功能特征的了解将导致对未来控制措施发展的重要展望。

Kaposi's sarcoma (KS) is a common AIDS-defining illness and epidemiological features suggest the involvement of a sexually transmitted agent in the etiology of AIDS-KS. The newly identified human herpesvirus-8 (HHV-8) is strongly associated in the etiology of non-AIDS and AIDS KS. Emerging serological studies suggest that seroprevalence of HHV-8 infections is low in the general U.S. population with a predominantly sexual mode of transmission. Our ongoing studies suggest that HHV-8 reactivation under reduced immuno-surveillence may precede the development of AIDS-KS. Effective future management of HHV-8 infections should incorporate control measurements such as active immunization against HHV-8. Our studies show that HHV-8 glycoproteins are good targets for human immune responses and suggest that eliciting immune response against HHV-8 envelope glycoproteins would provide an effective control against infection. Sequence data show that like other herpes viruses, HHV-8 encodes several glycoproteins. However knowledge about the identity, nature and functions of HHV-8 glycoproteins are limited and most of the available information comes from our ongoing studies. The overall objectives are to define the immunogenic envelope HHV-8 glycoproteins, to define their role in the biology of HHV-8 and to define the immune responses against them. By screening an HHV-8 cDNA library with an HIV+KS+ serum, cDNAs encoding glycoprotein gB (ORF8) and cDNAs originating from HHV-8 K8.1 gene have been identified. The K8.1 gene encodes two glycoproteins, K8.1A and B that are unique for HHV-8 and generated from spliced transcripts. Studies with human sera show that K8.1A and B are immunogenic glycoproteins. We hypothesize that ORF K8.1(A and B) and gB glycoproteins mediate important biological function(s). Our immediate focus now is to characterize the K8.1 and gB (ORF8) glycoproteins. We have formulated the following major specific aims: 1. To determine the presence and nature of K8.1(A and B) and gB glycoproteins in the infected cells and viral envelopes and to define their biochemical and structural properties. 2. To determine the role of K8.1(A and B) and gB glycoproteins in HHV-8 biology. 3. To determine the potential interactions of K8.1(A and B) and gB glycoproteins with host cell surface receptors(s) and to identify them. These studies are significant as the increased understanding of molecular, antigenic and functional characteristics of HHV-8 ORF K8.1(A and B) and gB will lead into an important in sight into the development of future control measures.