Pro-oncogenic, intra host viral quasispecies in Diffuse large B cell lymphoma patients with occult Hepatitis B Virus infection

Sci Rep. 2019 Oct 10;9(1):14516. doi: 10.1038/s41598-019-51157-1.

Abstract

Non Hodgkin lymphoma, predominantly Diffuse Large B-cell Lymphoma (DLBCL) has been reported to have a significant association with Hepatitis B virus (HBV). We investigated the presence of different gene segments of HBV in plasma, B-cells and tumor tissues from DLBCL patients and explored the genetic variability of HBV within and across different compartments in a host using Next Generation Sequencing. Despite all 40 patients being HBV seronegative, 68% showed evidence of occult HBV. Sequencing of these gene segments revealed inter-compartment viral variants in 26% of them, each with at least one non-synonymous mutation. Between compartments, core gene variants revealed Arg94Leu, Glu86Arg and Ser41Thr while X gene variants revealed Phe73Val, Ala44Val, Ser146Ala and Ser147Pro. In tumor compartments per se, several mis-sense mutations were detected, notably the classic T1762A/A1764G mutation in the basal core promoter. In addition, a virus surface antigen mis-sense mutation resulting in M125T was detected in all the samples and could account for surface antigen negativity and occult HBV status. It would be interesting to further explore if a temporal accumulation of viral variants within a favored niche, like patients' lymphocytes, could bestow survival advantage to the virus, and if certain pro-oncogenic HBV variants could drive lymphomagenesis in DLBCL.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • DNA, Viral / genetics
  • Genetic Variation
  • Hepatitis B / complications
  • Hepatitis B / virology*
  • Hepatitis B Surface Antigens / genetics
  • Hepatitis B virus / classification*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunohistochemistry
  • Lymphoma, Large B-Cell, Diffuse / virology*
  • Middle Aged
  • Mutation, Missense
  • Prospective Studies
  • Quasispecies*
  • Young Adult

Substances

  • DNA, Viral
  • Hepatitis B Surface Antigens