Zosteriform spread of herpes simplex virus as a model of recrudescence and its use to investigate the role of immune cells in prevention of recurrent disease.

During the development of a zosteriform rash, which occurs after flank inoculation of BALB/c mice with herpes simplex virus, clinically normal skin becomes infected via nerve endings. This is analogous to the final step in the development of a recrudescent lesion, which may occur after reactivation of latent virus. Therefore, the zosteriform reaction has potential as a model with which to study the modification of such a recrudescent infection by immune processes. Using an adoptive transfer system, we confirmed that immune lymph node cells are potent in accelerating the clearance of virus from the primary site of replication (the inoculation site). This effect was T cell dependent. However, if injection of the same cell population was delayed until ganglionic infection was established, the appearance of the zosteriform rash was not prevented, and the virus titer recovered from the lower flank was not reduced. Immunoperoxidase studies showed that virus is at first highly localized to the epidermis after it emerges from nerves. As determined by conventional histology, little cellular infiltration was seen until clinical lesions were apparent. These observations indicate that recrudescent lesions appear in the presence of cell populations normally associated with rapid virus clearance; cellular immune mechanisms may be rendered ineffective owing to the lack of recruitment to the site of recrudescence until tissue breakdown instigates an inflammatory response.