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Innate Immunity and Herpes Simplex Pathogensis

先天免疫和单纯疱疹发病机制

基本信息

批准号：
7877330
负责人：
Robert William Finberg
金额：
$ 2.07万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
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：
2009-07-14 至 2010-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7877330
关键词：
Affect Animal Model Biochemical Blood Cells CCL2 gene Cells Clinical Complex DNA Viruses Development Disease Embryo Encephalitis Event Failure Fibroblasts Genes Genetic Genetic Polymorphism Hand Herpes Labialis Herpes Simplex Infections Herpesvirus 1 Hospitals Human Immune response In Vitro Individual Infection Inflammatory Interferons Interleukin-6 Knock-out Knockout Mice Laboratories Lead Life Localized Disease Mediating Methods Modeling Mus Natural Immunity Neurons Newborn Infant Pathogenesis Pathway interactions Phase Population Production Proteins Reaction Recurrent disease Regulation Research Personnel Role Sampling Serum Signal Transduction Simplexvirus Sore Throat TLR2 gene TLR4 gene Testing Virus Virus Diseases Work animal model development cytokine mortality neonatal human neonate programs research study response virus genetics

项目摘要

DESCRIPTION (provided by applicant): Herpes simplex virus type 1 (HSV-1) is a complex DNA virus that causes life long infection in the majority of the world's population. In most people the disease is characterized by a primary illness that includes a sore throat and is variably followed by many years of asymptomatic carriage punctuated by occasional local reactions, usually occurring as "fever blisters." The virus is carried in its latent phase in neurons and may cause encephalitis. Newborn babies, on the other hand, present with a much different clinical picture that is characterized by either localized disease, encephalitis, or disseminated infection with a high mortality. Recent work in our laboratory has demonstrated that HSV induces the production of inflammatory cytokines through its interaction with TLR2. The same viruses also induce the production of interferon through TLR9. The mechanism by which HSV stimulates TLRs will be investigated using viral genetics and expression of isolated proteins. Using transfected cells and knockout mice we plan to define the pathways responsible for HSV induced cytokines and interferon and determine how TLRs affect both the immune response to HSV (using animal models), and the development of reactivation disease (in humans).

描述（由申请人提供）： 1 型单纯疱疹病毒 (HSV-1) 是一种复杂的 DNA 病毒，可导致世界上大多数人口终身感染。对于大多数人来说，这种疾病的特征是原发性疾病，包括喉咙痛，随后会出现多年的无症状症状，偶尔会出现局部反应，通常表现为“发烧水泡”。该病毒在潜伏期携带在神经元中，可能引起脑炎。另一方面，新生婴儿则呈现出截然不同的临床表现，其特征是局部疾病、脑炎或高死亡率的播散性感染。我们实验室最近的工作表明，HSV 通过与 TLR2 相互作用诱导炎症细胞因子的产生。同样的病毒还通过 TLR9 诱导干扰素的产生。 HSV 刺激 TLR 的机制将通过病毒遗传学和分离蛋白的表达进行研究。我们计划使用转染细胞和基因敲除小鼠来定义负责 HSV 诱导的细胞因子和干扰素的途径，并确定 TLR 如何影响 HSV 的免疫反应（使用动物模型）和再激活疾病的发展（在人类中）。