权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Spread of HSV-1 mediated by the gD receptor nectin-1

gD 受体 nectin-1 介导的 HSV-1 传播

基本信息

批准号：
7031532
负责人：
Robert James Geraghty
金额：
$ 25.17万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-09-30 至 2008-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7031532
关键词：
cadherins cell cell interaction cell fusion epithelium gene mutation herpes simplex virus 1 membrane proteins protein sequence tissue /cell culture transfection virus infection mechanism virus receptors

项目摘要

DESCRIPTION (provided by applicant): Herpes simplex virus (HSV) infection of epithelial cells often leads to spread of virus within the epithelium and to neurons for the establishment of a latent infection. Reactivation results in spread of virus from neurons back to epithelial cells. The virus can spread destructively in an epithelium, often in the presence of neutralizing antibody, resulting in the formation of a characteristic lesion. HSV spreads from an infected cell to an uninfected cell in three ways. First, extracellular virus binds cell-surface receptors on the adjacent cell and enters by fusion of the viral and cellular membranes (viral entry). Second, viral glycoproteins on the surface of the infected cell induce fusion with adjacent uninfected cells resulting in giant-multinucleated cells called syncytia (cell fusion). The third form of viral spread occurs between contiguous cells in the presence of neutralizing antibody and absence of syncytium formation (cell-cell spread). A cell-surface gD receptor, such as nectin-1, is required for all three forms of spread. The long term objective of these studies is to characterize the mechanisms of all three forms of nectin-1-dependent viral spread. We hypothesize that the structural features of nectin-1 that are critical for these three activities (and therefore the mechanisms) may differ, particularly for cell-cell spread. To test this hypothesis, we will identify domains of nectin-1 that are important for cell fusion and cell-cell spread. We will further characterize the mechanism of cell-cell spread by examining the functional requirements of adherens-junction proteins for efficient cell-cell spread in epithelial cells. The results of these studies, when compared and contrasted with previous work in viral entry, will elucidate nectin-1-mediated events at the cell membrane during viral spread. These results are important for the characterization of viral spread in an epithelium and may also be important for the characterization of spread of virus to neurons and interneuronal spread. Results from these studies will contribute to the understanding of viral spread in human and animal herpesviruses.

描述（由申请人提供）：上皮细胞的单纯疱疹病毒（HSV）感染通常导致病毒在上皮内扩散并扩散至神经元以建立潜伏感染。重新激活导致病毒从神经元传播回上皮细胞。通常在中和抗体存在的情况下，病毒可以在上皮细胞中破坏性传播，从而形成特征性病变。 HSV 通过三种方式从受感染的细胞传播到未受感染的细胞。首先，细胞外病毒与邻近细胞上的细胞表面受体结合，并通过病毒和细胞膜的融合进入（病毒进入）。其次，受感染细胞表面的病毒糖蛋白诱导与邻近未受感染细胞的融合产生称为合胞体（细胞融合）的巨型多核细胞。第三种形式的病毒传播发生在存在中和抗体且不存在合胞体形成的情况下（细胞间传播）的相邻细胞之间。所有三种形式的传播都需要细胞表面 gD 受体，例如 nectin-1。这些研究的长期目标是表征所有三种形式的 nectin-1 依赖性病毒传播的机制。我们假设对这三种活性（以及机制）至关重要的 nectin-1 的结构特征可能有所不同，特别是对于细胞间的扩散。为了检验这一假设，我们将确定对细胞融合和细胞间扩散很重要的 nectin-1 结构域。我们将通过检查上皮细胞中粘附连接蛋白有效细胞间扩散的功能要求，进一步表征细胞间扩散的机制。这些研究的结果与之前的病毒进入研究结果进行比较，将阐明病毒传播过程中 nectin-1 介导的细胞膜事件。这些结果很重要对于表征病毒在上皮中的传播，也可能对于表征病毒向神经元的传播和神经元间传播的表征也很重要。这些研究的结果将有助于了解人类和动物疱疹病毒的病毒传播。