Murine Leukemia viruses infect mice and cause various types of leukemias and also neurological diseases. The study of these viruses in genetically defined strains of mice provides a way to determine how virus/host interactions are important in disease, and provides clues about methods to prevent or treat human retroviral infections. We have been investigating the immune mechanisms involved in resistance to retroviral infections and found important roles for both antibody and cell-mediated immunity. We then developed a monoclonal antibody therapy to treat Friend Murine Leukemia Virus infections and discovered two host factors which influenced therapeutic efficacy. Our finding that the levels of CD4 positive T-cells in the host affected the efficacy of therapy has implications for similar therapies for HIV in humans. We also developed new knowledge regarding the immunological requirements for retroviral vaccines. Recombinant vaccinia virus vaccines with multiple T-helper and B-cell epitopes derived from viral envelope proteins primed for rapid IgG responses and protected mice from challenge in the absence of cytolytic T-lymphocytes (CTL). However, vaccines containing single T and B-cell epitopes could not protect in the absence of CTL, even though CTL epitopes were not required in the vaccine. In another study we created viruses containing chimeric envelope genes that allowed us to map viral determinants involved in virus induced neurological disease. We found two separate regions of envelope which could induce neurological disease independently from each other. Combination of the two neuropathogenic regions increased the tempo of disease but did not appear to affect the clinical signs. These studies may have relevance to HIV-associated dementia which also appears to be influenced by the type of envelope carried by the virus.
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