Herpes simplex virus (HSV) is the leading infectious cause of corneal blindness and visual impairment in the United States. Although a number of drugs have proven to be effective in treating acute infections none of the present agents can prevent recurrences of ocular herpes due to reactivation of latent virus residing within nerve tissue behind the eye. More basic research is needed on the various aspects of virus latency so that a rational strategy of therapy can be developed. One approach to analyzing the virus-neural cell interaction is to study how antibody influences the infection. Our recent efforts have established that non-neutralizing as well as neutralizing monoclonal antibodies passively transferred after HSV-1 corneal infection will suppress virus growth and enable mice to recover from infection. An additional finding is that trigeminal ganglions excised after infection in vivo exhibit a reduction in virus titer when incubated with conventional antibody or non-neutralizing monoclonal antibody specific for HSV glycoprotein A/B. We propose to exploit this trigeminal ganglion model to investigate some basic aspects of virus-neural cell interaction. Our initial goal is to define what antigen-antibody interactions lead to virus suppression. This will be studied using a battery of monoclonal antibodies to different HSV-1 antigenic determinants. Studies with isolated neuron and glial cells will enable us to identify the infected target cell(s) upon which antibody exerts its effect. By using immunoglobulin fragments we will determine whether inhibition involves antibody binding by the F(ab)2 region, the Fc region or both. Another objective is to determine where in the virus replication cycle the block occurs, i.e. in DNA or protein synthesis. Finally, the role of immune T cells in antibody-mediated virus suppression will be examined. This research will provide new understanding of the mechanism and consequences of antibody-mediated inhibition of HSV-1 growth in peripheral nervous tissue.
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