Avian reticuloendotheliosis virus (REV-T) is a replication-defective acute leukemia virus that transforms immature lymphocytes. REV-T stocks contain a replication-competent nontransforming helper virus (reticuloendotheliosis-associated virus: REV-A) that is present in 1000-fold excess. REV-A induces a suppressor cell population in the spleens of infected birds that can be detected within 3 days after virus infection. The suppressor cells prevent the proliferation of thymus-derived lymphocytes by a contact-mediated mechanism. We intend to define the mechanism by which REV-A induces this suppressor cell population. Replicating REV-A as well as other genetically related reticuloendotheliosis viruses induce this suppressor cell population, suggesting that the induction of suppressor cells may be mediated by a viral precursor polypeptide. REV-T nonvirus-producing transformed cells that do not contain viral precursor polypeptides but express a surface protein related to REV-A also induce suppressor cells. REV-A precursor polypeptides sharing sequences with the tumor cell antigen will be tested for their ability to induce suppressor cells and characterize the interaction between suppressor cells and immunoresponsive cells. Impairment of the cellular immune response is a general feature of the helper viruses of all known avian acute leukemia viruses. A number of experimental approaches will be employed to define whether helper virus-induced immunosuppression plays a significant role in the pathogenesis of viral-induced leukemia. The role of the helper virus-induced immunosuppression on the tumorigenicity and invasive properties of REV-T-transformed cells will be evaluated. (IS)

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA026169-08
Application #
3167206
Study Section
Experimental Immunology Study Section (EI)
Project Start
1979-07-01
Project End
1987-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
8
Fiscal Year
1986
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
Evans, R B; Gottlieb, P D; Bose Jr, H R (1993) Identification of a rel-related protein in the nucleus during the S phase of the cell cycle. Mol Cell Biol 13:6147-56
Bose Jr, H R (1992) The Rel family: models for transcriptional regulation and oncogenic transformation. Biochim Biophys Acta 1114:1-17
Storms, R W; Bose Jr, H R (1992) Alterations within pp59v-rel-containing protein complexes following the stimulation of REV-T-transformed lymphoid cells with zinc. Virology 188:765-77
Zhang, J Y; Olson, W; Ewert, D et al. (1991) The v-rel oncogene of avian reticuloendotheliosis virus transforms immature and mature lymphoid cells of the B cell lineage in vitro. Virology 183:457-66
Davis, J N; Bargmann, W; Bose Jr, H R (1990) Identification of protein complexes containing the c-rel proto-oncogene product in avian hematopoietic cells. Oncogene 5:1109-15
Davis, N; Bargmann, W; Lim, M Y et al. (1990) Avian reticuloendotheliosis virus-transformed lymphoid cells contain multiple pp59v-rel complexes. J Virol 64:584-91
Lim, M Y; Davis, N; Zhang, J Y et al. (1990) The v-rel oncogene product is complexed with cellular proteins including its proto-oncogene product and heat shock protein 70. Virology 175:149-60
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
Zhang, J Y; Bose Jr, H R (1989) Acquisition of new proviral copies in avian lymphoid cells transformed by reticuloendotheliosis virus. J Virol 63:1107-15

Showing the most recent 10 out of 21 publications