IMMUNE CONTROL OF EQUINE INFECTIOUS ANEMIA LENTIVIRUS

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The lentivirus subfamily of nononcogenic retroviruses has members that cause persistent infection of humans and animals resulting in progressive or recurrent disease. Even though the type of disease can include immunodeficiency, anemia, arthritis, encephalitis, and pneumonia, the lentiviruses share several biologic features. They are not eliminated from infected hosts and establish latent infection of host cells, particularly monocytes. Expression of lentiviruses by persistently infected host cells is enhanced by changes in the env gene sequence resulting in antigenic variants that escape the immune response. It is envisioned that the long range research goal of defining the molecular interactions between virus and lymphocytes that result in the control of a horse lentivirus, equine infectious anemia virus (EIAV), will provide valuable information for the control of human immunodeficiency virus and other animal lentiviruses. Horses with EIAV infection have recurrent episodes of clinical disease associated with cell-free viremia caused by unique antigenic variants. Most infected horses control each viremic episode within a few days after its appearance. Within a few months after infection, surviving horses uniquely control all occurrences of cell-free viremia and disease. It has been demonstrated that the control of EIA viremia is mediated by specific immune responses by infecting genetically immunodeficient horses with EIAV. To define the virus epitopes that stimulate the specific immune responses required to control EIAV, the hypothesis that the clinically-quiescent state in EIAV carriers is maintained by cytotoxic T lymphocytes and that this CTL response can be induced by immunization will be tested by pursuing 4 specific aims: 1. Inhibit EqCD8 lymphocyte function in EIAV carrier horses and determine if viremia and clinical disease occur. 2. Identify EIAV proteins and define epitopes recognized by CTL from carrier horses. 3. Induce CTL in horses with vaccinia virus recombinants expressing defined epitopes of EIAV proteins. 4. Challenge immunized horses with homologous EIAV and with antigeni variants.