Hepatitis virus-associated B cell non-Hodgkin’s lymphoma involves dysregulated epigenetic and RNA-mediated regulatory gene expression and altered snoRNA transcription

Infection with HBV and its satellite virus HDV remain a significant global health issue due to their involvement in hepatic and extrahepatic diseases, including B cell non-Hodgkin's lymphoma (BNHL). Clinical and epidemiological evidence support a causal role for HBV in BNHL development, although mechanistic insight is lacking and the role of HDV infection in this process is unknown. To help elucidate viral drivers of B cell transformation, we performed RNA-sequencing on peripheral B cells from patients with HBV mono-infection, HBV/HDV co-infection, HBV/HDV-associated BNHL, BNHL without viral infection, and healthy donors. In this way, we sought to identify unique and shared transcriptional profiles associated with viral infection and transformation. Our data suggest dysregulated epigenetic and miRNA-mediated regulatory gene expression may be a potential common pathway for lymphomagenesis among viral- and non-viral-associated lymphoma. We also observed wide-spread upregulation of snoRNAs in B cells from virally infected patients, supporting a role for these non-coding RNAs in viral infection and, potentially, viral-associated lymphomagenesis. These results have identified novel areas for future functional studies on the effect of HBV and HDV infection on B cell activity and present additional therapeutic strategies that may benefit both viral- and non-viral associated BNHL.