ASSEMBLY AND FUNCTION OF THE HERPES SIMPLEX ENVELOPE

疱疹病毒与一系列人类疾病有关；伯基茨 淋巴瘤和鼻咽癌(爱泼斯坦-巴尔病毒)，巨细胞 包涵体病(巨细胞病毒)、水痘和带状疱疹(水痘- 带状疱疹病毒)和口腔或生殖器粘膜皮肤损害(单纯疱疹 病毒、单纯疱疹病毒1型和2型)。他们保持潜伏，然后重新激活的能力 意味着它们在免疫后会出现严重的感染源 抑制器官移植、化疗对艾滋病患者的影响。最近的 抗阿昔洛韦的单纯疱疹病毒在CD4抑制人群中的出现 强调开发新的治疗策略的重要性 对抗疱疹病毒感染。 疱疹病毒是如何进入和离开细胞的，人们知之甚少。 感染过程中的包膜/质膜融合需要大量的 病毒蛋白，每种蛋白的分子作用尚不清楚。类似地， 新组装的子代衣壳被包裹的机制 目前还不清楚从牢房中释放的情况。这些措施的长期目标是 研究是对这些现象的分子解剖，揭示了关于 疱疹病毒的基本生物学和潜在的财富 新的病毒特异性药物靶点。具体目标如下： (1)。单纯疱疹病毒1型出血热的动力学和形态观察 被感染的细胞。一个单一的、同步的病毒粒子逃逸波将是 检测DNA包装、包膜、感染力和感染率 细胞的分泌物。针对病毒衣壳的抗体将是 用于将这些事件与形态现象相关联。 (2)。以确定HSV-1信封的来源。基本的单纯疱疹病毒 糖蛋白Gh将靶向于HSV感染细胞内的细胞器 确定包裹物的位置。病毒粒子通过亚细胞的途径 将对车厢进行监测，并确定出口的动力学。 (3)。鉴定Gh突变体tsQ26中的缺陷。脉冲追逐 实验将被用来检验GH的tsQ26等位基因的假设 无法流量到HSV包围站的不允许 温度。 (4)。鉴定融合所需的糖蛋白Gh区。区域 包膜/质膜融合所需的糖蛋白 细胞/细胞融合将使用瞬变 表达/互补试验。

Herpes viruses are associated with a range of human disease; Burkitts lymphoma and nasopharyngeal carcinoma (Epstein-Barr virus), cytomegalic inclusion disease (Cytomegalovirus), chickenpox and shingles (Varicella- Zoster virus) and oral or genital mucocutaneous lesions (Herpes simplex virus, HSV types 1 and 2). Their ability to remain latent, then reactivate means they present a serious source of infection following immune suppression in organ transplant, chemotherapy of AIDS patients. The recent appearance of acyclovir-resistant HSV strains in CD4-suppressed subjects underlines the importance of developing new therapeutic strategies to combat herpes virus infections. Little is known of how herpes viruses enter and leave cells. Envelope/plasma membrane fusion during infection requires a large number of viral proteins, and the molecular role of each is unknown. Similarly, the mechanism by which newly assembled progeny capsids become enveloped then released from the cell remains unclear. The long term objective of these studies is a molecular dissection of these phenomena, revealing much about the basic biology of the herpes viruses and potentially yielding a wealth of new virus-specific drug targets. The specific aims are as follows: (1). To investigate the kinetics and morphology of HSV-1 egress from infected cells. A single, synchronized wave of egressing virions will be assayed for DNA packaging, envelopment, acquisition of infectivity and rate of secretion from the cell. Antibodies against the viral capsid will be used to correlate these events with morphological phenomena. (2). To determine the origin of the HSV-1 envelope. The essential HSV glycoprotein gH will be targeted to organelles within HSV infected cells to identify the site of envelopment. Passage of virions through subcellular compartments will be monitored and the kinetics of egress determined. (3). To characterize the defect in the gH mutant tsQ26. Pulse chase experiments will be used to test the hypothesis that the tsQ26 allele of gH is unable to traffic to the site of HSV envelopment at the nonpermissive temperature. (4). To identify regions of glycoprotein gH required for fusion. Regions of the glycoprotein required for envelope/plasma membrane fusion and cell/cell fusion will be determined using a transient expression/complementation assay.