The role of the CMV-associated reactive oxygen species in age-related

CMV 相关活性氧在年龄相关性中的作用

• 批准号: 10313478
• 负责人: Kevin John Zwezdaryk
• 金额: $ 2.9万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-07 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10313478
• 关键词: role; CMV; associated; reactive; oxygen

Cytomegalovirus (CMV) infection is linked to increased risk of frailty and death in older populations. Despite being correlated to age-related disease, a mechanism linking CMV infection and unhealthy aging is unknown. We have recently reported that CMV infection alters mitochondrial structure and function promoting oxidative stress. CMV infection increases electron transport chain (ETC) activity resulting in elevate reactive oxygen species (ROS). Excess ROSis known to damage proteins and lipids and can induce mutations in mitochondrial DNA. Mitochondrial dysfunction is recognized as a hallmark of aging. This COBRE proposal is designed to identify mechanisms by which CMV exacerbates ROS leak, contributing to age-associated mitochondrial dysfunction. To test our hypothesis, we will integrate multiple model systems to delineate the role of CMV induced ROSon lipid peroxide levels (Specific Aim 1), the contribution of CMV-associated ROSproduction on endogenous mtDNA mutations (Specific Aim 2) and the contribution of lipid peroxides generated during CMV infection to exacerbate aged associated mitochondrial dysfunction (Specific Aim 3). CMV infection occurs for the lifetime of the host and reactivation is frequent throughout the hosts life. This suggests that oxidative stress may promote mitochondrial dysfunction that can accumulate over time. Our aims are designed to generate strong preliminary data to support NIH R01 grant applications. The manipulation of host mitochondria by CMV may clarify the role of CMV as a modulator that promotes unhealthy aging. Thus, fully understanding how a chronic viral infection can exacerbate aging represents a significant public health issue and novel therapeutic approach to both healthy aging and antiviral therapy.

巨细胞病毒（CMV）感染与老年人群的脆弱风险和死亡的风险增加有关。尽管与年龄相关的疾病相关，但连接CMV感染和不健康衰老的机制尚不清楚。我们最近报告说，CMV感染改变了线粒体结构和促进氧化应激的功能。 CMV感染增加了电子传输链（ETC）活性，导致活性氧（ROS）升高。已知会损害蛋白质和脂质的过多rosis，可以在线粒体DNA中诱导突变。线粒体功能障碍被认为是衰老的标志。该毛线建议旨在识别CMV加剧ROS泄漏的机制，从而导致与年龄相关的线粒体功能障碍。 To test our hypothesis, we will integrate multiple model systems to delineate the role of CMV induced ROSon lipid peroxide levels (Specific Aim 1), the contribution of CMV-associated ROSproduction on endogenous mtDNA mutations (Specific Aim 2) and the contribution of lipid peroxides generated during CMV infection to exacerbate aged associated mitochondrial dysfunction (Specific Aim 3). CMV感染发生在宿主的寿命中，并且在整个宿主寿命中经常进行重新激活。这表明氧化应激可能会促进可以随着时间的推移积累的线粒体功能障碍。我们的目标旨在生成强大的初步数据以支持NIH R01赠款应用程序。 CMV对宿主线粒体操纵可以阐明CMV作为促进不健康衰老的调节剂的作用。因此，充分了解慢性病毒感染如何加剧衰老是对健康衰老和抗病毒药疗法的重大公共卫生问题和新颖的治疗方法。