Distinctive EBV variants associated to pediatric benign and malignant pathologies: LMP1 sequence characterization and linkage with other viral gene polymorphisms

Abstract

The ubiquitous Epstein-Barr virus (EBV) is related to the development of lymphomas and is also the etiological agent for infectious mononucleosis (IM). Sequence variations in the LMP1 encoding gene have been deeply studied in different pathologies and geographic regions. Controversial results propose the existence of tumor-related variants while others argued in favor of a geographical distribution of these variants. However, current reports assessing EBV variants in IM were performed in adult patients who display multiple variant infections. In the present study, LMP1 variants in 15 pediatric patients with IM and 20 pediatric EBV-associated lymphomas from Argentina were compared as representatives of benign and malignant infection in children, respectively. A three months follow-up study of LMP1 variants in peripheral blood cells and in oral secretions of patients with IM was performed. Moreover, an integrated linkage analysis was performed with variants of EBNA1 and the promoter region of BZLF1. Similar sequence polymorphisms were detected in both pathological conditions, IM and lymphoma, but these differ from those previously described in healthy donors from Argentina and Brazil. The results suggest that certain LMP1 polymorphisms, namely the 30bp deletion and high copy number of the 33bp repeats, could be associated to EBV-related pathologies, either benign or malignant instead of just tumor related. Additionally, this is the first study to describe the Alaskan variant in EBV-related lymphomas previously restricted to nasopharyngeal carcinomas from North America..