DELAYED HYPERSENSITIVITY TO HERPES SIMPLEX VIRUS

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This project will continue to investigate delayed hypersensitivity (DH) to herpes simplex virus (HSV) in mice to further clarify the role of this cell-mediated immune response in protection against HV infection and establishment of latency. Our approach will use a model system we have developed in mice where animals are infected or immunized with virus or viral proteins. Delayed hypersensitivity is assessed by challenging the mice with virus or protein in the ears and measuring increased ear swelling with an engineer's micrometer. Protection and latency is assessed in a model system where nonprotected mice die from lethal HSV infection within 10 days. The mouse model provides an excellent system where different functional T cell subsets can be identified and easiy manipulated. We propose to isolate HSV glycoproteins from infected cells and test these proteins, together with chemical and/or enzymatic fragments, for their ability to induce DH and protective immunity. We will also synthesize synthetic peptides which correspond to selected portions of the glycoprotein molecules and test these peptides for induction of DH and protective immunity. In addition we will explore aspects of experimental tolerance to HSV by characterizing certain types of suppressor cells previously identified and evaluate HSV infected mice for the presence of suppressor cells. Our purpose here is to determine if, during active infection, HSV induces suppressor cells which limit the immune response thus favoring the establishment of chronic or latent infection. Finally we propose to establish a series of HSV glycoprotein-specific T cell clones. These clones will be characterized and used in vitro to examine the fine specificity of the HSV glycoproteins which induce protective DH responses. The importance of DH in immune protection against HSV infection is still poorly understood. Our studies should provide useful information for future development of improved treatment protocols using immunopotentiators and/or active immunization.