The Molecular Pathogenesis of Varicella Zoster Virus Infection

水痘带状疱疹病毒感染的分子发病机制

基本信息

批准号：
9306675
负责人：
Maria Acena Nagel
金额：
$ 7.75万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-03-01 至 2019-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9306675
关键词：
Acquired Immunodeficiency Syndrome Acute Adrenal Cortex Hormones Adult Age Aging American Animal Model Antiviral Agents Awareness Biopsy Blindness Blood C-reactive protein CD8-Positive T-Lymphocytes Cell Communication Cells Cellular Immunity Chickenpox Clinical DNA biosynthesis Data Development Diagnosis Disease Doctor of Philosophy Elderly Epigenetic Process Event Exanthema Flow Cytometry Ganglia Genes Genetic Transcription Genome Goals Headache Herpes zoster disease Herpesviridae Herpesvirus Type 3 Human Immune Immune response Immunity Immunocompromised Host Immunologics Incidence Infection Jaw Laboratories Latent Virus Lung Malignant Neoplasms Methods Modeling Molecular Molecular Immunology Molecular Virology Monkeys Morbidity - disease rate Myalgia Neuraxis Neurology Neurons Organ Organ Transplantation Pain Paralysed Pathogenesis Pathologic Pathway interactions Patients Population Postherpetic neuralgia Primary Infection Process Role Sedimentation process Severities Steroids Stroke Temporal Arteries Temporal Arteritis Testing Therapeutic Intervention Tissues Translating Transplant Recipients Vaccinated Vaccines Viral Pathogenesis Virus Virus Diseases base cell type chronic neurologic disease chronic pain claudication clinical practice dermatome design innovation lymph nodes mortality nervous system disorder neurotropic novel prevent programs public health relevance skills success targeted treatment transcriptome varicella zoster virus vasculopathy viral DNA virus host interaction virus pathogenesis

项目摘要

DESCRIPTION (Provided by applicant): The goal of this program project (PPG) is to prevent serious neurological disease in the elderly caused by reactivation of the ubiquitous highly neurotropic varicella zoster virus (VZV). The PPG contains 3 scientific projects and supportive administrative and scientific cores. Primary infection by varicella zoster virus (VZV) usually causes varicella, after which virus becomes latent in ganglionic neurons along the entire neuraxis. With aging, a declining cell-mediated immunity to VZV leads to virus reactivation, manifesting as herpes zoster (shingles) characterized by pain and rash restricted to 1-3 dermatomes. The incidence and severity of zoster is also increased in organ transplant recipients and patients with cancer or AIDS. Zoster is frequently complicated by chronic pain (postherpetic neuralgia), paralysis, blindness and stroke. Currently, -1,000,000 Americans develop zoster annually. Oka VZV vaccine reduces the incidence of zoster by 50%, but even if every American over age 60 was vaccinated, >500,000 cases would still occur every year. This PPG will: determine the emerging role of multifocal VZV vasculopathy as an important cause of vision loss and headaches in the elderly, examine mechanisms by which VZV exits latency to cause disease and identify key virus-host interactions involved in immunity and spread of infection. Project 1, an exciting new translational project, will identify clinical, laboratory and pathological features of a form of multifocal VZV vasculopathy that mimics giant cell arteritis (GCA), a cause of vision loss and headache in the elderly, findings that are likely to shift the current clinical practice paradigm. Project 2 tests the hypothesis that VZV reactivation initially involves generalized deregulation of latent gene transcription followed by conditions conducive to virus DNA replication and release of infectious virus. Project 3 uses an animal model to determine critical virus-host immune cell interactions that contribute to viral pathogenesis. The combined studies will provide valuable clinical, laboratory and pathological data needed to diagnose and treat a form of multifocal VZV vasculopathy that mimics giant cell arteritis and will provide the needed molecular groundwork for efforts to prevent the cascade of events leading to VZV reactivation, a cause of serious neurologic disease, particularly in the rapidly increasing elderly and immunocompromised populations. This proposal melds the skills and strategies of MDs, PhDs and DVMs with expertise in clinical neurology, molecular virology and immunology.

描述（由申请人提供）：该计划项目（PPG）的目的是预防由无处不在的高度神经性高神经素素皮带轮病毒（VZV）引起的老年人的严重神经系统疾病。 PPG包含3个科学项目以及支持性的行政和科学核心。水痘带状疱疹病毒（VZV）的原发性感染通常会引起水疗，此后病毒在整个神经神经术的神经节神经元中变得潜在。随着衰老的衰老，对VZV的细胞介导的免疫力下降会导致病毒重新激活，表现为疱疹带状疱疹（带状疱疹），其特征是疼痛，皮疹限制在1-3个皮肤上。在器官移植受者和癌症或艾滋病患者中，带状线的发病率和严重程度也会增加。带状疱疹经常因慢性疼痛（后神经痛），瘫痪，失明和中风而复杂。目前，每年-1,000,000美国人开发带状绿色。 OKA VZV疫苗将带领的发病率降低了50％，但即使为60岁以上的每个美国人接种疫苗，仍将每年发生> 500,000例病例。该PPG将：确定多灶性VZV血管病的新兴作用是老年人视力丧失和头痛的重要原因，检查VZV消除潜伏期引起疾病并识别引起疾病的关键病毒 - 宿主相互作用的机制，并鉴定出与感染和传播有关的关键病毒 - 霍斯特相互作用。项目1是一个令人兴奋的新翻译项目，将确定临床，实验室和多灶性VZV血管病的病理特征，即模仿巨细胞动脉炎（GCA）是老年人视力丧失和头痛的原因，可能会改变当前的临床实践范式。项目2检验了VZV重新激活的假设最初涉及对潜在基因转录的普遍放松管制，然后是有利于病毒DNA复制和释放感染性病毒的条件。项目3使用动物模型来确定有助于病毒发病机理的关键病毒宿主免疫细胞相互作用。合并的研究将为诊断和治疗模仿巨型细胞动脉炎的多焦VZV血管病的一种有价值的临床，实验室和病理数据，并为防止级联的VZV重新疗效的事件提供了所需的分子角度，尤其是在严重的神经系统疾病中，尤其是在快速增加的老年人中，并为造成了严重的神经系统疾病的概括。该建议将MDS，PHD和DVM的技能和策略与临床神经病学，分子病毒学和免疫学方面的专业知识融合在一起。