HUMAN CYTOMEGALOVIRUS AND CELL PROLIFERATION CONTROL

人类巨细胞病毒和细胞增殖控制

• 批准号: 6081167
• 负责人: JONATHAN P CASTILLO
• 金额: $ 1.76万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-25 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6081167
• 关键词: Adenoviridae; Herpesviridae disease; cell cycle; cell growth regulation; cell line; cell proliferation; complementary DNA; cytomegalovirus; gene expression; genetic transcription; immediate early protein; p53 gene /protein; recombinant virus; regulatory gene; restenosis; vascular smooth muscle; western blottings

Recent studies have suggested a link between some cases of restenosis and the herpesvirus, human cytomegalovirus (HCMV). A closer examination revealed that this relationship correlated with HCMV immediate early (IE) gene expression in restenosis lesions and the stabilization and inactivation of the p53 tumor suppressor. These observations suggest a hypothesis that restenosis is caused by p53 inactivation by HCMV infection or other events that down regulate p53 activity. We propose to further examine the relationships between the HCMV IE gene products, p53, and cell proliferation control. We will examine whether HCMV IE gene expression contributes to the overproliferation of smooth muscle cells observed in restenosis. We will address these issues by employing a powerful approach, which utilizes replication, defective, recombinant adenoviruses to transiently introduce and express genes of interest. By using this approach, we propose: (1) to determine the extent to which HCMV IE gene expression affects cell cycle regulation; (2) to determine the biochemical mechanisms by which HCMV IE gene expression affects cell cycle - alteration of RB and p53 functions; and (3) to examine the effects of HCMV IE gene expression on early passage arterial smooth muscle cells. Together, these experiments will clarify the role of HCMV infection in restenosis.

最近的研究表明，一些再狭窄病例与疱疹病毒、人类巨细胞病毒（HCMV）之间存在联系。 更仔细的检查表明，这种关系与再狭窄病变中的 HCMV 即早期 (IE) 基因表达以及 p53 肿瘤抑制因子的稳定和失活相关。 这些观察结果表明，再狭窄是由 HCMV 感染或其他下调 p53 活性的事件引起的 p53 失活引起的。 我们建议进一步研究 HCMV IE 基因产物 p53 与细胞增殖控制之间的关系。 我们将检查 HCMV IE 基因表达是否有助于再狭窄中观察到的平滑肌细胞过度增殖。我们将通过采用一种强大的方法来解决这些问题，该方法利用复制、有缺陷的重组腺病毒来瞬时引入和表达感兴趣的基因。 通过使用这种方法，我们建议：（1）确定HCMV IE基因表达影响细胞周期调控的程度； (2)确定HCMV IE基因表达影响细胞周期的生化机制——RB和p53功能的改变； (3)检测HCMV IE基因表达对早期传代动脉平滑肌细胞的影响。总之，这些实验将阐明 HCMV 感染在再狭窄中的作用。