mRNA-seq of wild-type or p53-deficient B cells expressing MHV68 M2
Gammaherpesviruses (GHV) are DNA tumor viruses that establish lifelong latent infections in lymphocytes. For viruses such as Epstein-Barr virus (EBV) and murine gammaherpesvirus 68 (MHV68), this is accomplished through a viral gene-expression program that promotes cellular proliferation and differentiation, especially of germinal center (GC) B cells. Intrinsic host mechanisms to control virus-driven cellular expansion are incompletely defined. Using a small-animal model of GHV pathogenesis, we identify the B cell-specific latency gene M2, an MHV68 mediator of GC B cell differentiation, as a viral gene product that is sufficient to induce p53 in a manner that is dependent on Src kinase activity. To understand the function of M2 in primary B cells, we performed retroviral transduction of M2 or M2.Stop in wild-type or p53-deficient B cells. Our results reveal p53 and cellular proliferation pathways enriched in M2-expressing B cells. Overall design: Comparative gene expression profiling analysis of RNA-seq data for retrovirally transduced primary B cells with MHV68 M2, a FSS mutant, M2.Stop, or EBV LMP1