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. We performed RNA-sequencing on peripheral B cells from patients with HBV mono-infection, HBV/HDV co-infection, BNHL, and HBV/HDV-associated BNHL to identify unique and shared transcriptional profiles associated with 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. Overall design: RNA-sequencing of peripheral B cells isolated from patients with chronic HBV infection (n=4), HBV/HDV co-infection (n=7), B cell non-Hodgkin's lymphoma (n=6), HBV/HDV-associated B cell non-Hodgkin's lymphoma (n=3), and healthy donors (n=6)