MODULATION OF TUMOR NECROSIS FACTOR BY ADENOVIRUS

腺病毒对肿瘤坏死因子的调节

• 批准号: 2857534
• 负责人: JORDAN PATRICK METCALF
• 金额: $ 11.65万
• 依托单位: UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-30 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2857534
• 关键词: adeno associated virus group; chloramphenicol acetyltransferase; clone cells; enzyme activity; enzyme linked immunosorbent assay; gel mobility shift assay; gene expression; genetic promoter element; genetic regulation; genome; lung disorder; messenger RNA; pathology; plasmids; polymerase chain reaction; tissue /cell culture; transcription factor; transfection; tumor necrosis factor alpha

Acute adenoviral infection has been associated with severe lung disease. Chronic sequelae may also result from adenoviral infection, such as hyperlucent lung syndrome and chronic obstructive lung disease. Various cytokines, especially tumor necrosis factor (TNF) appear to be necessary for the development of many acute and chronic lung diseases. Since the early genes of adenovirus are expressed during latency and during acute infection, the regulation of cytokine production by -these genes may be important in the pathogenesis of both acute and chronic sequelae of adenoviral infection. The purpose of this proposal is to advance our understanding of the mechanisms by which adenovirus regulates the TNF gene. We will first assess whether adenovirus early genes can upregulate the TNF gene. Next, we will examine the mechanism of this regulation both from the standpoint of the viral genome and from the standpoint of the TNF gene itself. Finally, we will assess whether or not these same mechanisms are important in the regulation of TNF by whole adenovirus following acute infection of human inflammatory cell lines in vitro.

急性腺病毒感染与严重的肺部疾病有关。 慢性后遗症也可能是由腺病毒感染引起的 超韧性肺综合征和慢性阻塞性肺疾病。各种各样的 细胞因子，尤其是肿瘤坏死因子（TNF）似乎是必要的 为了发展许多急性和慢性肺部疾病。自从 腺病毒的早期基因在潜伏期和急性期间表达 感染，这些基因可能是细胞因子产生的调节 在急性和慢性后遗症的发病机理中很重要 腺病毒感染。该提议的目的是促进我们的 了解腺病毒调节TNF的机制 基因。我们将首先评估腺病毒早期基因是否可以上调 TNF基因。接下来，我们将研究这一法规的机制 从病毒基因组的角度，从TNF的角度来看 基因本身。最后，我们将评估这些相同的机制是否 急性后，整个腺病毒对TNF的调节很重要 体外感染人类炎症细胞系。

项目成果

Tumor necrosis factor-alpha activation by adenovirus E1A 13S CR3 occurs in a cell-dependent and cell-independent manner.

腺病毒E1A 13S CR3对肿瘤坏死因子-α的激活以细胞依赖性和细胞非依赖性的方式发生。

• DOI: 10.1152/ajplung.00342.2001
• 发表时间: 2002
• 期刊: American journal of physiology. Lung cellular and molecular physiology
• 作者: Sanchez,TraciA;Booth,JLeland;Metcalf,JordanP
• 通讯作者: Metcalf,JordanP

Zinc finger and carboxyl regions of adenovirus E1A 13S CR3 are important for transactivation of the cytomegalovirus major immediate early promoter by adenovirus.

腺病毒 E1A 13S CR3 的锌指和羧基区域对于腺病毒反式激活巨细胞病毒主要立即早期启动子非常重要。

• DOI: 10.1165/ajrcmb.23.5.3675
• 发表时间: 2000
• 期刊: American journal of respiratory cell and molecular biology.
• 作者: Sanchez,TA;Habib,I;LelandBooth,J;Evetts,SM;Metcalf,JP
• 通讯作者: Metcalf,JP