CELLULAR HOMOLOGS OF HERPESVIRUS GENES

疱疹病毒已经发展出对抗宿主防御的策略，因此 至于允许病毒感染细胞并导致潜伏或持久的 感染。该项目的目标是确定和确定 疱疹病毒蛋白与宿主细胞蛋白相互作用的功能 来影响感染的进程。这些蛋白质可能会让我们 识别在人类免疫系统中重要的新分子。 程序性细胞死亡(细胞凋亡)是一种抗病毒防御机制 由宿主清除受病毒感染的细胞。一些病毒编码 干扰细胞凋亡信号通路的蛋白质。我们 发现两种DNA病毒，传染性软疣病毒和马 疱疹病毒2型编码具有死亡效应结构域(DED)的蛋白质。 含有DEDS的细胞蛋白介导了细胞凋亡信号通路。 然而，与细胞蛋白不同的是，含有DED的病毒蛋白 抑制细胞凋亡。这些病毒蛋白可以直接与 细胞蛋白质并通过抑制它们的活性可能允许 病毒感染的细胞可以逃脱细胞凋亡。 EB病毒感染B淋巴细胞，引起传染性 单核细胞增多症，与某些人类肿瘤有关。EBV编码 一种称为GP42的膜蛋白。我们发现GP42与一种蛋白质结合 对免疫系统的识别很重要(MHC II类人类白细胞抗原-DR β链)，并抑制EBV转化的B细胞的生长。一个 含有GP42的融合蛋白也抑制了几种免疫活性 (抗原的呈递和抗原特异性细胞毒的产生 混合淋巴细胞培养中的T淋巴细胞)。由于GP42与MCH绑定 存在于B淋巴细胞表面的II类人类白细胞抗原-DR，GP42 EBV与B淋巴细胞结合或穿透可能是重要的。

Herpesviruses have developed strategies to counteract host defenses so as to allow viruses to infect cells and result in a latent or persistent infection. The goal of this project is to identify and determine the function of herpesvirus proteins that interact with host cell proteins to influence the course of infection. These proteins may allow us to identify new molecules that are important in the human immune system. Programmed cell death (apoptosis) is an antiviral defense mechanism used by the host to eliminate virus-infected cells. Some viruses encode proteins that interfere with signalling pathways for apoptosis. We found that two DNA viruses, molluscum contagiosum virus and equine herpesvirus 2, encode proteins with death effector domains (DEDs). Cellular proteins containing DEDs mediate apoptosis signalling pathways. However, unlike the cellular proteins, the viral DED-containing proteins inhibit apoptosis. These viral proteins can bind directly to the cellular proteins and by inhibiting their activity may allow virus-infected cells to escape apoptosis. Epstein-Barr virus (EBV) infects B lymphocytes, causes infectious mononucleosis, and is associated with certain human tumors. EBV encodes a membrane protein termed gp42. We found that gp42 binds to a protein important for recognition by the immune system (the MHC class II HLA-DR beta chain) and inhibits the outgrowth of EBV transformed B cells. A fusion protein containing gp42 also inhibited several immune activities (presentation of antigens and generation of antigen-specific cytotoxic T lymphocytes in mixed lymphocyte cultures). Since gp42 binds to MCH class II HLA-DR, which is present on the surface of B lymphocytes, gp42 may be important for EBV to bind to or penetrate B lymphocytes.