Retroviruses that cause disease in humans have been identified recently. Since our understanding of immune response to these viruses, especially cellular immune responses, is rudimentary, it is imperative to study immunity to retroviruses in model systems. The studies supported by this grant are directed toward elucidation of the cellular immune response in mice to the retroviruses that comprise the Friend erythroleukemia virus complex (FV). We have developed a system in which individual molecularly cloned viruses of this complex (F-MuLV, SFFV and F-MCF), as well as individual molecularly cloned genes of each virus, can be introduced into and expressed in cells of a rat fibroblast line. When appropriate murine class I major histocompatibility molecules are also introduced into each cell line, the cells become potential targets for cytotoxic T lymphocytes (CTL) generated by immunizing mice with cells infected by the same molecularly cloned viruses of the FV complex. Analysis of the patterns of reactivity of different CTL populations on different """"""""synthetic"""""""" target lines will identify the components of the virus involved in target structures recognized by the CTL. We will also identify particular regions of the viral genes encoding epitopes for CTL recognition by constructing mutant viral genes for analysis. We will construct a packaging-deficient mutant of the helper component of FV complex in order to produce virus particles free of RNA for studies of their capacity to immunize against infectious virus.
| Ruan, K S; Lilly, F (1992) Approach to a retrovirus vaccine: immunization of mice against Friend virus disease with a replication-defective Friend murine leukemia virus. Proc Natl Acad Sci U S A 89:12202-6 |
| Ruan, K S; Lilly, F (1991) Identification of an epitope encoded in the env gene of Friend murine leukemia virus recognized by anti-Friend virus cytotoxic T lymphocytes. Virology 181:91-100 |
| Polsky, D; Lilly, F (1991) Suppression of H-2b-associated resistance to Friend erythroleukemia virus by a class I gene from the H-2d major histocompatibility complex haplotype. Proc Natl Acad Sci U S A 88:9243-7 |
| Hoatlin, M E; Kozak, S L; Lilly, F et al. (1990) Activation of erythropoietin receptors by Friend viral gp55 and by erythropoietin and down-modulation by the murine Fv-2r resistance gene. Proc Natl Acad Sci U S A 87:9985-9 |
| Holt, C A; Osorio, K; Lilly, F (1986) Friend virus-specific cytotoxic T lymphocytes recognize both gag and env gene-encoded specificities. J Exp Med 164:211-26 |
