Infection with equine infectious anemia virus vaccine strain EIAV(DLV121) causes no visible histopathological lesions in target organs in association with restricted viral replication and unique cytokine response

The live equine infectious anemia virus (EIAV) vaccine strain EIAV(DLV121) was developed by in vitro attenuation of a virulent strain, EIAV(LN40), in the 1970s, and it has been demonstrated to induce protective immunity under laboratory and natural EIAV infection conditions. The detailed biological features of this attenuated virus remain to be further investigated. Experimental inoculation with EIAV(DLV121) did not result in clinical symptoms even with immunosuppressive treatment in our previous studies. Here, we further investigated whether the replication of the vaccine strain EIAV(DLV121) in experimentally infected horses causes histopathological lesions to develop in the targeted organs. Both the lungs and the spleen have been demonstrated to support EIAV replication. By evaluating the gross macroscopic and histological changes, we found that EIAV(DLV121) did not cause detectable histopathological lesions and that it replicated several hundred times more slowly than its parental virulent strain, EIAV(LN40), in tissues. Immunochemical assays of these tissues indicated that the primary target cells of EIAV(DLV121) were monocytes/macrophages, but that EIAV(LN40) also infected alveolar epithelial cells and vascular endothelial cells. In addition, both of these viral strains promoted the up- and down-regulation of the expression of various cytokines and chemokines, implicating the potential involvement of these cellular factors in the pathological outcomes of EIAV infection and host immune responses. Taken together, these results demonstrate that the EIAV vaccine strain does not cause obvious histopathological lesions or clinical symptoms and that it induces a unique cytokine response profile. These features are considered essential for EIAV(DLV121) to function as an effective live vaccine.