TRANSMISSION OF HERPES SIMPLEX ACROSS CELL JUNCTIONS

单纯疱疹病毒(HSV)可以从 在上皮和神经元组织中，一个细胞与另一个相邻细胞。这个 属性似乎涉及病毒颗粒在细胞内的运输 细胞间的连接或接触。病毒糖蛋白Ge和Gi 是HSV在细胞间有效传播所必需的，但不是 细胞外病毒进入所需的。因此，HSVGE和GI和 其他疱疹病毒中的同源物似乎选择性地作用于细胞对... 细胞在进入细胞外过程中扩散，而不是在细胞表面 病毒。这是蛋白质在体内发挥作用的唯一例子 举止。GE/GI也被认为是一种免疫球蛋白Fc受体活性，但 这一属性似乎与便利的能力无关 细胞到细胞的传输。我们发现GE/GI定位于 特异性地定位于上皮细胞的外侧表面，共定位 具有附着的结点并被排除在紧密结点之外，并且是 不存在于不与其他细胞接触的细胞的侧面 细胞。这表明Ge/Gi具有与细胞结合的能力 结成分，从而在细胞结合处发生积累。它 我的假设是GE/GI与细胞配体的结合集中在 促进病毒在细胞间转移的细胞连接。这个 本研究的目的是通过以下方式来研究分子机制 单纯疱疹病毒在细胞间传播。我们将研究这一关系 在细胞-细胞扩散和细胞结合处Ge/Gi的积累之间， 细胞中表达的GE/GI是否能饱和细胞配体并阻断 细胞-细胞的扩散，作用于各种细胞连接成分和细胞 黏附分子(CAM)在这一过程中，并试图识别 Ge/Gi的细胞配体。这些研究不仅应该揭示 这种病毒如何与细胞连接相互作用，但也提供了有价值的 关于细胞连接的细胞生物学的新信息。正直的人 细胞连接对维持渗透性屏障很重要 也使分化和生长调节的正常过程 都得到了维护。在行进过程中会丢失凸轮或CAM适配器 一种更恶性的表型。CAM或CAM适配器，例如APC、DCC和 钙粘附素是已知的肿瘤抑制因子，它们的缺失导致 分化程度较低且更易移动或转移的表型。我 希望我们对HSV与细胞相互作用的研究 交汇点将具有重要意义，提供有关 特定的CAM与病毒传播的关系和更好的 了解CAM如何在细胞和组织中发挥作用。

Herpes simplex viruses (HSV) can spread very efficiently directly from one cell to a neighboring cell, in epithelial and neuronal tissues. The property appears to involve transport of virus particles across cell junctions or contacts made between cells. Viral glycoproteins gE and gI are necessary for efficient spread of HSV between cells but are not required for entry of extracellular virus. Therefore, HSV gE and gI and homologues in other herpesviruses appear to selectively act in cell-to- cell spread and not at the cell surface during entry of extracellular viruses. This the only example of proteins which function in this manner. gE/gI has also been ascribed an IgG-Fc receptor activity, but this property appears to be unrelated to the capacity to facilitate cell-to-cell transmission. We have found that gE/gI localizes specifically to the lateal surfaces of epithelial cells, colocalizing with adherens junctions and being excluded from tight junctions, and is not present on those lateral surfaces of cells not in contact with other cells. This suggests that gE/gI has the capacity to bind to cell junction components so that accumulation at cell junctions occurs. It is my hypothesis that gE/gI binds to cellular ligands concentrated at cell junctions to promote transfer of virus between cells. The objectives of this research are to examine the molecular mechanisms by which HSV spreads from cell-to-cell. We will study the relationship between cell-cell spread and accumulation of gE/gI at cell junctions, whether gE/gI expressed in cells can saturate cell ligands and block cell-cell spread, the role of various cell junction components and cell adhesion molecules (CAMs) in this process, and attempt to identify cellular ligands of gE/gI. These studies should shed light not only on how this virus interacts with cell junctions but also provide valuable new information on the cell biology of cell junctions. The integrity of cell junctions is important to maintain a permeability barrier and also so that the normal course of differentiation and growth regulation are maintained. Loss of CAMs or CAM adaptors occurs during progression to a more malignant phenotype. CAMs or CAM adaptors, e.g. APC, DCC, and cadherins, are known to act as tumor suppressors and their loss leads to a less differentiated and more motile or metastatic phenotype. I expect that our studies of the interactions between HSV and cell junctions will have significance, providing new information on the relationship between specific CAMs and virus spread and a better understanding of how CAMs function in cells and tissues.