Analysis of Epstein-Barr virus infection in short-term pediatric carriers as a risk for early lymphoma development

VISTAROP A; COHEN, M; DE MATTEO E; PRECIADO MV; PAOLA ANDREA CHABAY

Montreal

Congreso; DNA Tumor Virus Meeting 2016; 2016

Epstein-Barr virus (EBV) is acquired silently early in life and established as an asymptomatic infection of the B cells However, the delicate EBV-host balance could be disturbed and the virus displays its pathogenic potential. The reasons why EBV is involved on the development of tumors are still under discussion. In Argentina primary infection is mostly subclinical at young age, and EBV-associated lymphomas prevail in patients younger than 10 years. Therefore, it represents an interesting population to analyze EBV infection and the relationship with lymphomas. The aim of this study was to characterize EBV infection in a group of pediatric patients, by localizing histological regions of viral protein expression, and assessing B-cell-infected subpopulation in tonsil biopsies. Viral antigen presence in subepithelial (SubEp) and interfolicular (IF) lymphocytes were observed at young age.Latency(L)III was prevalent and related to the germinal center(GC), while LII was associated with non-GC(p=0.0159, 2test). In older patients EBV was detected at GC and epithelial cells. This finding is sustained by viral load, which was higher at the SubEp-IF regions and decreased when EBV was not expressed at the SubEp region (p=0.0236, Mann Whitney test). Cases with EBERs+/CD27+ or EBERs+/IgD+ cells exhibited a trend to lower mean age and confirmed that EBV infection models, GC (target IgD+ B-cell) and direct infection (target memory B-cell) models, are not mutually exclusive. During acute infection, EBV from saliva exchanged with another infected individual enters the tonsil crypts and crosses the thin layer of epithelium overlying the lymphocytes below. In our series, viral antigens are expressed at SubEp and IF cells at younger age, denoting that probably the virus has recently entered and it is allowed to express the full latent antigen profile, LIII. While in older patients EBV presence was detected at the GC region and in epithelial cells, perhaps because they have been infected a long time ago, and the virus can spread, specifically from epithelial cells. The LIII pattern prevailed in our series, so it should be considered that the synergism of oncogenic viral proteins could be involved in B-cell lymphoma development in young children in our population. This analysis will shed light on some aspects of EBV pathogenesis, in order to assess if viral protein expression and occasional transformation process could eventually arise as a complication of early infection.