v-rel induces expression of three avian immunoregulatory surface receptors more efficiently than c-rel

Abstract

The c-rel gene is a member of NF-KBIrel family of transcription factors that regulate expression of a variety of immunoregulatory molecules. The virat oncogene, v-rel, is a truncated and mutated form of the turkey c-rel gene expressed by reticuloendotheliosis virus, strain T. In this study, we demonstrated that three avian immunoregulatory receptors, major histocompatibility (MHC) antigens class I and class II as well as the interleukin-2 receptor (IL-2R), were induced on the surface of splenic tumor cells isolated from chickens infected with reticuloendotheliosis virus, strain T. All cell lines derived from splenic tumors expressed these three proteins. Their expression also correlated with the appearance of endogenous c-rel during a graft-versushost reaction. In vitro, both c-rel and v-rel induced MHC class I, MHC class II, and IL-2R on an avian B-lymphoid cell line, DT95, and a T-lymphoid cell line, MSB-1. Quantitative kinetic analysis demonstrated both the accumulation of MHC class II mRNA and the appearance of surface MHC class II protein in response to the synthesis of either v-rel or c-rel. We show that v-rel induced the expression of MHC class II in the avian B-cell lines DT40 and DT95 more rapidly than c-rel and that, several weeks after infection, v-rel induced MHC class II as much as 50-fold more efficiently than c-rel. Finally, in vitro infection of splenocytes with retroviruses that express v-rel or c-rel induced MHC class I, MHC class II, and IL-2R expression. Quantitative analysis confirmed that p59v-re was consistently more efficient at inducing expression of all three immunoregulatory receptors than exogenous p68c-er. These data suggest that during tumor development, v-rel functions to induce (or suppress) the expression of genes similarly induced (or suppressed) by c-rel. The observations reported in this study are not in agreement with a model in which v-rel promotes tumor development by functioning as a dominant negative mutant of c-rel. In contrast, these findings support the hypothesis that lymphocyte immortalization and tumor development are the result, at least in part, of the capacity of v-rel to function as a dominant positive mutant that induces expression of genes normally regulated by c-rel.

The relocalization of v-Rel from the nucleus to the cytoplasm coincides with induction of expression of Ikba and nfkb1 and stabilization of I kappa B-alpha

“…All recombinant DNA techniques were performed by conventional methods (77). Construction of pREV-0, pREV-TW, pREV-C, and pCSV11S3 has been described previously (44,69). pREV-TW plasmid contains v-rel (15) cloned into an REV-T-based vector, REV-0.…”

“…Transfection of CEF with plasmids containing different retroviral genomes was performed by a modified calcium phosphate method as described previously (14). Infectious titers of helper CSV and replication-defective viruses were determined by a modified immunocytochemical assay with monoclonal antibodies HY83, HY87, and HY95 (44,84).…”

“…We have demonstrated previously that v-Rel induces the surface expression of major histocompatibility complex (MHC) classes I and II as well as the interleukin-2 receptor (IL-2R) on the avian B-cell line DT95 and the T-cell line MSB-1 more efficiently than c-Rel does (44). In this study we demonstrate that the increased induction of these immunoregulatory proteins by v-Rel was accompanied by a partial relocalization of v-Rel protein from the nucleus to the cytoplasm.…”

NF-κB c-Rel Dictates the Inflammatory Threshold by Acting as a Transcriptional Repressor

“…c-Rel stands for the cellular homolog of v-Rel, a protein encoded in avian reticuloendotheliosis virus strain T (Rev T) (Capobianco et al, 1990;Carrasco et al, 1996). It is thought that v-Rel was acquired by Rev T via horizontal transfer of turkey c-Rel and that subsequent mutations resulted in structural alterations in v-Rel ( Figure 2D) and lent v-Rel its high oncogenic potential (Hrdlickova et al, 1994). v-Rel and c-Rel have previously been shown to possess the ability to transcriptionally repress RelA, using HIV-kB and IL-2-kB promoter sites (Ballard et al, 1990.…”

Virus-induced immunosuppression in turkeys (<i>Meleagris gallopavo</i>): A review

“…Tumors induced by the REV are associated to the B cells (Woźniakowski et al, 2018). Damage of T cells, reduction of lymphocyte T in peripheral blood, and suppression of splenic cells have been documented in chickens (Hrdlicková et al, 1994;Bi et al, 2018). The decreased number of T-cells might be responsible for the lower levels of IL8 and IL18 (Bi et al, 2018).…”