EYE INFECTIONS BY TYPE 2 HERPES SIMPLEX VIRUS

2 型单纯疱疹病毒引起的眼部感染

基本信息

批准号：
3256029
负责人：
JANG O OH
金额：
$ 15.09万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
1976
资助国家：
美国
起止时间：
1976-09-30 至 1989-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3256029
关键词：
Alphaherpesvirinae acyclovir antibody specificity antiviral agents herpes simplex virus 2 histopathology immunoglobulin G lymphocyte macrophage mature animal newborn animals serotyping tissue /cell culture virus classification virus cytopathogenic effect

项目摘要

The pathogenic mechanism for herpetic chorioretinitis in the neonate is poorly understood. Our preliminary studies in the newborn rabbit revealed that a) mononuclear cells infected with type 2 herpes simplex virus (HSV-2), rather than free HSV-2, produce retinochoroiditis; b) HSV-2 induced Fc receptors for normal IgG on mononuclear cells; and c) mononuclear cells infected with HSV-2 required normal IgG for the induction of the ocular lesion in the newborn rabbits. Based on these observations, as well as those of other researchers, the following pathogenic process for the development of retinochoroiditis in the neonate is proposed: Following infection, HSV-2 induces Fc receptors for normal IgG on the mononuclear cells. The binding of IgG to the Fc receptors changes the nature of the cell surface of HSV-infected mononuclear cells and leads to the entrapment of the cell in the capillaries of the retina and choroid. The entrapped HSV-infected mononuclear cell then initiates infection at the site and produces retinochoroiditis. To examine the validity of this proposed pathogenic process, the following series of experiments will be carried out: a) subpopulations of mononuclear cells which are major carriers of HSV-2 and are capable of producing retinochoroiditis in the newborn rabbits will be determined; b) the interaction between HSV-2 and mononuclear cells will be studied, and HSV-induced Fc receptors on the mononuclear cells will be characterized; c) the effects of binding of IgG to HSV-induced Fc receptors on the HSV-infected mononuclear cells and on the induction of retinochoroiditis will be evaluated. Finally, (d) the effect of HSV-specific antibody and of the antiviral agents on the HSVG-infected mononuclear cells will be tested. If the validity of this hypothesis can be proven, our investigation will have important medical implications: a) The pathogenic process for neonatal herpetic retinochoroiditis will be clarified, and an effective means of preventing and treating the disease will be found; b) the biological role of Fc receptors in the pathogenesis of herpetic retinochoroiditis will be identified; and c) the findings of this investigation will shed some light in our understanding of pathogenesis of retinochoroiditis in the newborn produced by other viruses, such as varicella-zoster, cytomegalo, measles and rubella viruses.

新生儿疱疹性绒毛膜炎的致病机制为理解不佳。我们在新生兔子的初步研究表明 a）被2型疱疹的单纯疱疹病毒感染的单核细胞（HSV-2）而不是游离HSV-2会产生视网膜性炎； b）HSV-2 单核细胞上正常IgG的诱导FC受体；和c）感染HSV-2的单核细胞需要正常的IgG诱导新生兔子的眼病变。基于这些观察，以及其他研究人员的提出了新生儿视网膜炎的发展：以下感染，HSV-2诱导正常IgG的FC受体在单核上细胞。 IgG与FC受体的结合改变了 HSV感染的单核细胞的细胞表面，并导致陷阱视网膜和脉络膜毛细血管中的细胞。被困的然后，HSV感染的单核细胞在现场引发感染，并产生视网膜炎。为了检查该提出的致病过程的有效性，以下将进行一系列实验：a）单核细胞是HSV-2的主要载体，能够将确定新生兔子中产生视网膜性炎； b）将研究HSV-2和单核细胞之间的相互作用，并将表征HSV诱导的单核细胞上的FC受体。 c） IgG与HSV诱导的FC受体的结合对 HSV感染的单核细胞和视网膜炎的诱导将进行评估。最后，（d）HSV特异性抗体和将测试HSVG感染的单核细胞上的抗病毒剂。如果可以证明该假设的有效性，我们的调查将具有重要的医学意义：a）新生儿疱疹性视网膜性炎将被澄清，有效将发现预防和治疗疾病的手段； b） FC受体在疱疹发病机理中的生物学作用视网膜类炎将被鉴定出来；和c）这一发现调查将使我们对其他病毒产生的新生儿中的视网膜智炎，例如水痘带状疱疹，巨细胞，麻疹和风疹病毒。