The Centers for Disease Control has recently observed that old individuals who receive transfusions of HIV infected blood develop symptoms of AIDS more quickly than young individuals who receive comparable transfusions. The most apparent explanation for this increased susceptibility to development of AIDS is that introduction of HIV into an environment that already demonstrates a certain level of immunosuppression results in more rapid manifestations of HIV-induced immunosuppression and, thus development of AIDS. However, other explanations are also possible. Although the ideal situation would be to examine the differences in susceptibility in humans, these studies are difficult to perform due to the small number of individuals >60 who have been infected with HIV and the great differences in environmental exposure of old individuals and young individuals. Due to these difficulties in experimental design, studies to investigate both the degree and mechanism of altered susceptibility of old individuals to HIV must be examined in an animal model. The retrovirus, Friend leukemia virus (FLV) in mice was chosen for these studies due to the availability of information and reagents regarding the immune system, changes in the immune system with age and FLV. Further, HIV has a genome and life cycle and causes severe immunosuppression similar to FLV. In the proposed studies we will determine: 1. Differences in susceptibility of old and young mice to a. FLV-induced disease b. FLV-induced immunosuppression 2. The mechanism of differences in susceptibility of old and young mice to FLV-induced disease. 3. The mechanism(s) of FLV-induced immunosuppression in both young and old mice. These studies will provide information regarding not only differences in susceptibility of old and young individuals to retrovirus induced disease and immunosuppression, but also the mechanism(s) of retrovirus-induced immunosuppression in all ages of individuals.
