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）：单纯疱疹病毒1型（HSV-1）是一种复杂的DNA病毒，可在世界大多数人群中引起寿命长期感染。在大多数人中，这种疾病的特征是一种原发性疾病，其中包括喉咙痛，随后是多年的无症状马车，偶尔会出现局部反应，通常以“发烧水泡”的形式出现。该病毒在神经元的潜在阶段携带，可能引起脑炎。另一方面，刚出生的婴儿的临床表现截然不同，其特征是局部疾病，脑炎或传播感染，并具有高死亡率。我们实验室的最新工作表明，HSV通过与TLR2的相互作用诱导炎症细胞因子的产生。相同的病毒还通过TLR9诱导干扰素的产生。将使用病毒遗传学和分离蛋白的表达研究HSV刺激TLR的机制。使用转染的细胞和基因敲除小鼠，我们计划定义负责HSV诱导细胞因子和干扰素的途径，并确定TLR如何影响对HSV的免疫反应（使用动物模型）以及重新激活疾病的发展（在人类中）。