p300 promotes cell proliferation through suppressing Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation in the infected B-lymphoma cells

Abstract

Primary Effusion Lymphoma (PEL) is a B-cell lymphoma associated with Kaposi's sarcoma herpesvirus (KSHV) infection. However, the mechanism of oncogenesis of PEL is still unclear. Studies have shown that the cellular transcriptional coactivator p300 regulates the interaction between host and virus, which plays a vital role in viral replication. In this study, we investigated the role of p300 in BCBL1 cells during the KSHV life cycle. We found that p300 knockout resulted in an overall increase for the early lytic genes and changed the expression of genes associated with tumor development, proliferation, and the immune response in the KSHV infected B cells. However, knockout of p300 significantly inhibited the expression of the immediate-early gene RTA and the late lytic gene K8 after KSHV lytic activation. Additionally, the intracellular KSHV genome copy number and the virion production were reduced. These results demonstrated that p300 plays a crucial role in suppressing KSHV viral replication in BCBL1. Furthermore, we observed that the growth of BCBL1 was inhibited by knockout of p300, which confirmed our findings that p300 promotes cell proliferation. This study further provided evidence that p300 plays an important role in the pathogenesis of BCBL1, which might lead to the oncogenesis of PEL caused by KSHV infection.

Keywords: BCBL1; KSHV; RNA-seq; p300.