Avian reticuloendotheliosis virus (REV-T) is a replicatoin - defective retrovirus which transforms very immature lymphoid cells and induces a fatal lymphoma within 7-10 days. REV-T co- replicates with a genetically related replication-competent virus reticuloendotheliosis associated virus, REV-A. REV-A induces a rapid suppression of the cellular immune response. REV-A induces or activates a non-antigen specific T suppressor cell which impairs mitogen-induced blastogenesis, mixed lymphocyte response, allograft rejection, and cell mediated cytotoxic response. REV-A has a sequence within its p20E envelope protein which shares extensive homology with the envelope sequence of other retroviruses which induce cell killing and immunosuppression. REV-T transformed nonvirus-producing (NP) cells also induce or activate a T suppressor cell which inhibits lymphocyte blastogenesis by a contact mediated mechansim. REV-T does not encode a p20E protein. We propose to determine whether the p20E envelope protein of REV-A is involved in immunosuppression. We will synthesize a peptide corresponding to this region and assess its ability to kill cells and activate suppressor cells in vitro and in vivo. If REV-T tumor cells and REV-A induce suppressor cells by the same mechanism, a product of the gag cistron is likely to be involved since gag is the only viral cistron shared by the two viruses. We have constructed a collection of molecularly cloned REV-T proviral DNA sequences which contain deletions in defined regions of the gag cistron. These deletion mutants will be packaged and used to transform spleen cells. REV-T transformed NP cells containing these deletions will be evaluated for their ability to immunosuppress. In addition to defining which viral sequence is involved in immunosuppression, we will also determine whether a cellular product antigenically related to p20E is produced by immunosuppressive REV-T transformed cells. If the REV-T transformed cells produce this peptide, we will determine whether a viral gene product (gag) or proviral integration activates this cellular immunoregulatory gene. The final objective of this proposal will be to isolate and characterize the suppressor cells induced by REV-A or by the injection of REV-T transformed NP lymphoid cells to establish whether both the virus and tumor cells activate the same suppressor cell population.
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