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

VISTAROP A; DE MATTEO E; PRECIADO MV; PAOLA ANDREA CHABAY

Trieste

Congreso; ICGEB DNA tumour virus meeting 2015; 2015

ICGEB

The Epstein Barr virus (EBV) was the first human virus associated to malignancy, even though in most carriers it behaves as a harmless passenger.The reasons why some of them develop EBV-associated neoplasias still remains unknown. In order to characterize EBV biology and its possible involvement with lymphoma development, viral infection was previously studied in adults with primary infection and healthy carriers. In Argentina primary infection is mostly subclinical at young age, and EBV-associated B-cell lymphomas prevail in patients younger than 10 years. Therefore, it represents an interesting population to analize EBV infection. Tonsil biopsies in short-term pediatric carriers were studied, to characterize EBV infection, to localize histological regions of latent and lytic viral protein expression, and to assess B cell-infected subpopulation.Latency II (LII) was statistically associated with non GC region, while latency III (LIII) was predominant and related to GC (p= 0.0159; Chi2 test). Viral antigen presence in the subepithelial and IF lymphocytes at young age was established, where probably the virus has recently got access and it displays the LIII. In contrast, EBV presence in the GC region and in epithelial cells, where the virus can spread, are observed in older patients, perhaps because they have been infected time ago.This finding is also sustained by viral load, which is higher at the subepithelial and IF regions and decreases when EBV is not expressed at the subepitelial region (p=0.0236 M-W test). The majority of cases displayed EBERs+/IgD+ cells (p=0.0021; Chi2 test),with high viral load but without specfic association with age. Patients with EBERs+/CD27+ cells exhibited a trend to lower median age. Given that LIII pattern prevailed in our series, the oncogenic potential of those viral proteins, particularly EBNA3A and LMP1, expressed together could be involved in pediatric B cell lymphomagenesis at young age observed in Argentina. 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 primary infection. In addition, infection of naïve B cells along with viral protein expression prevalent in the IF region, confirms that both EBV infection models are not mutually exclusive in our population.