The role of viral-specific immunity and cytotoxic T lymphocyte avidity in the control of equine infectious anemia virus

The purpose of this study was to test the hypothesis that viral-specific immunity and high avidity cytotoxic T lymphocytes (CTL) are important in the control of equine infectious anemia virus (EIAV). In the first experiment, immune reconstitution was attempted prior to EIAV challenge in 2 severe combined immunodeficient foals, using adoptively transferred virus-stimulated lymphocytes derived from persistently EIAV-infected half sibling donors. Following transfer, lymphocyte engraftment occurred in 1 foal, and EIAV-specific CTL as well as neutralizing antibody activity developed. EIAV replication was controlled in this foal and plasma virus could not be detected by reverse transcriptase-polymerase chain reaction or culture. These results provide direct evidence that a specific immune response is required for EIAV control. In the second experiment, memory CTL (CTLm) responses were analyzed in 2 EIAV-infected horses with high plasma viral loads and recurrent disease (progressors), and in 2 EIAV-infected horses with low to undetectable viral loads and minimal disease (nonprogressors). Unexpectedly, high avidity CTLm were detected in both progressors, while only moderate to low avidity CTLm were detected in the nonprogressors. High avidity CTLm in one progressor recognized an epitope in the highly variable principle neutralizing domain of envelope gp90, and the data documented for the first time in EIAV that viral variation within the epitope led to escape of CTLm recognition. Each of the nonprogressors had moderate to low avidity CTLm directed against epitopes within peptides containing the nuclear export and nuclear localization domains of Rev. It was concluded that CTI-m avidity does not correlate with control of viral load and clinical disease in EIAV-infected horses, but that the epitopes recognized by CTLm likely are more important in determining disease outcome.