Characterization of Borna disease virus-mediated antagonization of the cellular interferon system

博尔纳病病毒介导的细胞干扰素系统拮抗作用的表征

• 批准号: 5395208
• 负责人: Privatdozent Dr. Thorsten Wolff
• 金额: --
• 依托单位: Fachgebiet 17: Influenzaviren und weitere Viren des Respirationstraktes
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2003
• 资助国家: 德国
• 起止时间: 2002-12-31 至 2005-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5395208?language=en
• 关键词: Characterization; Borna; disease; virus; mediated

The type I interferon (IFN) system is one of the most important mediators of the innate response of vertebrates toward virus infections. It is triggered most likely by double-strand (ds) RNA produced during viral replication which is recognized by cellular sensor proteins. The neurotropic Borna Disease Virus (BDV) possesses a non-segmented negative strand RNA genome that is replicated in the cell nucleus. Although BDV replication leads potentially to the production of dsRNA, the virus can successfully establish persistent, non-cytolytic infections of tissue culture cells and in certain animal species. Thus, BDV can resist or avoid the deleterious effects of the innate response, but the mechanism of this escape is unknown. I have discovered that a BDV infection suppresses the ability of cells to respond to stimuli that activate the IFN system. This finding demonstrates that BDV expresses a gene product(s) that interferes with the signaling processes required for induction of type I IFN genes. Reporter gene assays have indicated that at least one BDV-specific protein exhibits such an acitivity. The goals of this project are to identify and to characterize the precise IFN antagonistic protein of BDV and to decipher the mechanisms underlying this activity. It is expected that we will gain novel mechanistical insights how Borna viruses and possibly other viral pathogens counteract the innate response and cause disease.

I型干扰素系统是脊椎动物对病毒感染先天应答的重要介质之一。它最有可能是由病毒复制过程中产生的双链(DS)RNA触发的，这种RNA被细胞传感器蛋白识别。嗜神经性博尔纳病病毒(BDV)具有在细胞核内复制的非节段性负链RNA基因组。虽然BDV的复制可能导致dsRNA的产生，但该病毒可以成功地在组织培养细胞和某些动物物种中建立持续的、非细胞溶解的感染。因此，BDV可以抵抗或避免先天反应的有害影响，但这种逃逸的机制尚不清楚。我发现BDV感染会抑制细胞对激活干扰素系统的刺激做出反应的能力。这一发现表明，BDV表达一种基因产物(S)，该基因产物干扰诱导I型干扰素基因所需的信号传递过程。报告基因分析表明，至少有一种BDV特异性蛋白具有这种活性。本项目的目标是鉴定和鉴定BDV的干扰素拮抗蛋白，并破译该活性的机制。预计我们将获得新的机制洞察力，博纳病毒和可能的其他病毒病原体如何抵消先天反应并导致疾病。