Innate Immunity and Herpes Simplex Pathogensis

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。在大多数人中，这种疾病的特征是原发性疾病，包括喉咙痛，然后是多年的无症状携带，偶尔出现局部反应，通常发生为“发热水泡”。“这种病毒在潜伏期携带在神经元中，可能导致脑炎。另一方面，新生儿的临床表现则大不相同，表现为局限性疾病、脑炎或死亡率高的播散性感染。我们实验室最近的工作表明，HSV通过与TLR 2相互作用诱导炎性细胞因子的产生。相同的病毒也通过TLR 9诱导干扰素的产生。HSV刺激TLR的机制将使用病毒遗传学和分离蛋白的表达来研究。使用转染的细胞和基因敲除小鼠，我们计划定义负责HSV诱导的细胞因子和干扰素的途径，并确定TLR如何影响对HSV的免疫应答（使用动物模型）和再活化疾病的发展（在人类中）。

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).