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.
Showing the most recent 10 out of 11 publications
