Interactions between equine herpesvirus type 1 and equine herpesvirus type 4: T cell responses in a murine infection...

Interactions involving the immune responses to equine herpesvirus types 1 and 4 (EHV-1 and EHV-4) were studied in a murine infection model. When mice were inoculated intranasally with EHV-1, virus replication occurred in the respiratory tract and clinical signs were produced. In contrast, mice that were similarly inoculated with EHV-4 produced no evidence of virus replication and showed no clinical signs. When mice that had been inoculated with live EHV-4 were challenged 1 month later with EHV-1 they were partially protected. Although clinical signs were apparent on reinfection, virus replication in the respiratory tract was reduced in these mice compared with control mice that had not been previously immunized. Mice primed with heat-inactivated EHV-4, however, were not so protected. Live EHV-4-primed mice developed very low levels of antibody to EHV-1 and the humoral response could not account for this protection. However, the infected mice did give a strong delayed-type hypersensitivity reaction in a skin test using either EHV-1 or EHV-4 antigen. Spleen cells from EHV-4-primed donors provided a source of immune cells, including T cells which were used for transfer to recipient mice which were then challenged with EHV-1. The cells were protective; there was a reduction of virus replication on challenge with EHV-1 which correlated with the number of cells transferred. Modulation of the protective effect of primed cell populations was tested after depletion in vivo by means of complement-mediated lysis. The depletion of CD4-bearing cells produced the least effect on the protection afforded by cell transfer. In contrast, depletion of CD8-bearing cells markedly reduced the protection in recipients. EHV-1 and EHV-4 are widespread in horses and cross-infections are common. These results gained from a murine model indicate that important interactions occur at the level of T cell immunity between the two virus types which warrant further investigation in the natural host.