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.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
2R01CA026169-09
Application #
3167204
Study Section
Experimental Immunology Study Section (EI)
Project Start
1979-07-01
Project End
1992-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
9
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Texas Austin
Department
Type
Schools of Arts and Sciences
DUNS #
City
Austin
State
TX
Country
United States
Zip Code
78713
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Ulug, E T; Garry, R F; Bose Jr, H R (1989) The role of monovalent cation transport in Sindbis virus maturation and release. Virology 172:42-50
Moore, B E; Bose Jr, H R (1989) Expression of the c-rel and c-myc proto-oncogenes in avian tissues. Oncogene 4:845-52
Zhang, J Y; Bargmann, W; Bose Jr, H R (1989) Rearrangement and diversification of immunoglobulin light-chain genes in lymphoid cells transformed by reticuloendotheliosis virus. Mol Cell Biol 9:4970-6

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