Chicken lncRNA-9802 Induces the S Phase Arrest in the T Lymphocyte Cells Infected by Marek's Disease Virus via the TP53BP1/p53/p21 Pathway.

The oncogenic Marek's disease virus (MDV) triggers Marek's disease (MD), which is a substantial threat to poultry as it transforms infected T cells into tumors. Our research identified that long non-coding RNA 9802 (lncRNA-9802) exhibits increased expression in the chicken spleen following MDV infection, with its expression being strongly associated with the expression of tumor p53-binding protein 1 (TP53BP1). The function of lncRNA-9802 in T cells transformed by MDV remains unclear. Consequently, the expression levels of lncRNA-9802 were either over-expressed or knocked down in MDV-transformed T cells, MDCC-MSB1, through lentivirus-mediated over-expression and knock down experiments. Our findings demonstrate that lncRNA-9802 induces proliferation disturbances in MDCC-MSB1 cells by causing arrest in the S phase, which is accompanied by increased expression levels of TP53BP1, p53, and p21. Activation of the p53 pathway results in elevated levels of Cyclin E and Cyclin-dependent kinase 2 (CDK2), thereby facilitating the entry of MDCC-MSB1 cells into the S phase. Concurrently, the reduced levels of Cyclin A inhibit the exit of MDCC-MSB1 cells from the S phase. By modulating the TP53BP1/p53/p21 pathway, lncRNA-9802 induces S phase arrest in MDCC-MSB1 cells, characterized by upregulation of Cyclin E and CDK2 and downregulation of Cyclin A. This research enhances the understanding of the pathogenic mechanisms of MDV and provides a foundation for identifying potential targets for antiviral drug development.