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

Authors

• AN Henning
• ND Dashdorj
• NJ Dashdorj
• V De Giorgi

Abstract

Globally, an estimated 296 million people are living with chronic hepatitis B virus (HBV) infection, with ~4.5% co-infected with the satellite virus, hepatitis delta (HDV). While these viruses are known to contribute to hepatic diseases, and eventually hepatocellular carcinoma, their role in B cell non-Hodgkin’s lymphoma (BNHL) is not confirmed. Chronic inflammation and immune system dysregulation caused by chronic infection may contribute to an increased risk of lymphoma indirectly. To help elucidate the role for HBV and HDV infection in the development of BNHL, RNA-sequencing was performed on peripheral B cells collected from patients with chronic HBV mono-infection, HBV/HDV co-infection with or without BNHL, BNHL-only patients, and healthy donors. We observed increased expression of several epigenetic regulatory genes across all disease groups, including components of the SWI/SNF and NuRD chromatin remodeling complexes and the COMPASS histone methyltransferase complex. We also saw upregulation of genes involved in RNA-mediated regulation, specifically genes encoding components of the RISC complex. In peripheral B cells from chronically infected patients, we observed an upregulation of small nucleolar RNAs (snoRNAs) that was correlated with expression of ribosome biogenesis factors and ribosomal subunits. This was especially pronounced in HBV mono-infection patients. Our results suggest that dysregulated epigenetic and RNA-mediated gene expression may be an early factor of lymphomagenesis common to non-viral and viral-mediated BNHL. Additionally, chronic HBV/HDV co-infection and, especially, chronic HBV mono-infection results in altered snoRNA expression with potential impacts on ribosome biogenesis and subunit composition. This may represent a viral-specific mechanism contributing to lymphoma development.

Scientific Focus Area: Cancer Biology

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