EBNA1 sequences in Argentinean pediatric acute and latent Epstein-Barr virus infection reflect circulation of novel South American variants

Abstract

Epstein-Barr virus (EBV) is related to the development of lymphomas and is also the etiological agent for infectious mononucleosis (IM). Sequence variation of the EBNA1 gene, consistently expressed in all EBV-positive cells, has been widely studied. Based on the amino acid at codon 487 five major EBNA1 variants have been described, two closely related prototypic variants (P-ala and P-thr) and three variant sequences (V-leu, V-val, and V-pro). Sub-variants were then further classified based on mutations other than the originally described. While several studies proposed associations with tumors and/or anatomical compartments, others argued in favor of a geographical distribution of these variants. In the present study, EBNA1 variants in 11 pediatric patients with IM and 19 pediatric EBV lymphomas from Argentina were compared as representatives of benign and malignant infection in children, respectively. A 3-month follow-up study of EBNA1 variants in peripheral blood cells and in oral secretions of patients with IM was performed. A new V-ala variant which includes five V-ala sub-variants and three new V-leu sub-variants was described. These data favor the geographical association hypothesis since no evidence for a preferential compartment distribution of EBNA1 variants and sub-variants was found. This is the first study to characterize EBNA1 variants in pediatric patients with infection mononucleosis worldwide.