The biological properties of different Epstein-Barr virus strains explain their association with various types of cancers

Abstract

The Epstein-Barr virus (EBV) is etiologically associated with the development of multiple types of tumors, but it is unclear whether this diversity is due to infection with different EBV strains. We report a comparative characterization of SNU719, GP202, and YCCEL1, three EBV strains that were isolated from gastric carcinomas, M81, a virus isolated in a nasopharyngeal carcinoma and several well-characterized laboratory type A strains. We found that B95-8, Akata and GP202 induced cell growth more efficiently than YCCEL1, SNU719 and M81 and this correlated positively with the expression levels of the viral BHRF1 miRNAs. In infected B cells, all strains except Akata and B95-8 induced lytic replication, a risk factor for carcinoma development, although less efficiently than M81. The panel of viruses induced tumors in immunocompromised mice with variable speed and efficacy that did not strictly mirror their in vitro characteristics, suggesting that additional parameters play an important role. We found that YCCEL1 and M81 infected primary epithelial cells, gastric carcinoma cells and gastric spheroids more efficiently than Akata or B95-8. Reciprocally, Akata and B95-8 had a stronger tropism for B cells than YCCEL1 or M81. These data suggest that different EBV strains will induce the development of lymphoid tumors with variable efficacy in immunocompromised patients and that there is a parallel between the cell tropism of the viral strains and the lineage of the tumors they induce. Thus, EBV strains can be endowed with properties that will influence their transforming abilities and the type of tumor they induce.

Natural Variation of Epstein-Barr Virus Genes, Proteins, and Primary MicroRNA

“…The different properties of EBV isolated from carcinomas, particularly M81 EBV from an NPC patient, have been proposed to be consistent with EBV in this region being more likely to cause NPC (20–22). Sequence differences between Asian and western EBV strains have been known for some time (2, 23), and our previous principal-component analysis (2) pointed to several regions of the EBV genome that distinguish Asian EBV strains from other EBVs.…”

Latency and lytic replication in Epstein–Barr virus-associated oncogenesis

“…In addition to polymorphisms in the BZLF1 promotor, polymorphisms in the BZLF1 gene might also account for higher lytic EBV replication. Along these lines, the M81 EBV strain isolated from a nasopharyngeal carcinoma sample and three EBV isolates from gastric carcinomas induced increased spontaneous lytic EBV replication in B cells and epithelial cells 80,81 . M81 BZLF1, but not BZLF1 from EBV B95-8 that was isolated from an American individual with infectious mononucleosis, was able to induce this elevated lytic replication in the M81 EBV background, when provided in trans 80 .…”

Epstein‐Barr virus strain variation and cancer

“…The M81 virus and other epithelial cancer‐derived EBV strains show high propensities to infect epithelial cells . Epitheliotropism is apparently advantageous for the virus to increase the chance to infect the nasopharyngeal epithelium.…”

“…60 The M81 virus and other epithelial cancer-derived EBV strains show high propensities to infect epithelial cells. 45,62 Epitheliotropism is apparently advantageous for the virus to increase the chance to infect the nasopharyngeal epithelium. The viral gB protein (gp110) of the M81 strain is at least partly responsible for the enhanced tropism toward epithelial cells ( Figure 5).…”