Epstein Barr Virus Lytic Cycle Involvement In Diffuse Large B Cell Lymphoma

COHEN, M; VISTAROP A; HUAMAN F; NARBAITZ, M; METREBIAN, F; DE MATTEO E; PRECIADO MV; PAOLA ANDREA CHABAY

HEMATOLOGICAL ONCOLOGY

JOHN WILEY & SONS LTD

Lugar: LOndres; Año: 2018 vol. 7 p. 98 - 103

0278-0232

It has been largely demonstrated that EBV mediated B cell transformation is predominantly achieved through the action of latent proteins, but recent evidence suggests that lytic EBV replication has also a certain pathogenic role in lymphomagenesis, at least in the early phases of cell transformation. Particularly, in DLBCL, EBV lytic cycle is by and large unexplored, so in order to disclose lytic cell contribution to lymphomagenesis, our aim was to evaluate viral early and late lytic gene expression in relation to several immune response markers in a series of EBV+ DLBCL from Argentina. An unexpected number of cells expressed lytic transcripts, being transcribed at the BZLF1, BHRF1 and BLLF1 locus, by RT- qPCR. This lytic antigen expression was confirmed by immunohistochemical staining for BMRF1 early lytic protein, and a positive correlation between lytic and latent genes was confirmed, revealing a close link between their expressions in DLBCL pathogenesis. Remarkably, BZLF1 displayed a statistically negative correlation with CD4 cell counts, and this could be in part justified by the restriction of antigen presentation previously reported. The direct statistical correlation for the late lytic gene BLLF1 and IFN in this series could represent a specific response directed towards this antigen. IL-10 transcripts also displayed a positive correlation with lytic expression, indicating that regulatory mechanisms could be involved on EBV-associated DLBCL pathogenesis in our series. Complete lytic reactivation in EBV-positive tumors could potentially kill EBV-positive malignant cells, providing a tool to promote tumor cell killing mediated by EBV as a new treatment strategy.