A novel recombinant variant of latent membrane protein 1 from Epstein Barr virus in Argentina denotes phylogeographical association.

Magdalena Gantuz,María Victoria Preciado,Mario Alejandro Lorenzetti,Paola Andrea Chabay,Edward Gershburg

doi:10.1371/journal.pone.0174221

Abstract

Epstein Barr virus (EBV) infection in Argentina occurs at an early age and occasionally develops infectious mononucleosis (IM). EBV is also related with lymphomas. LMP1, the viral oncoprotein is polymorphic and is used to define viral variants.AimTo study LMP1 variants distribution among children with EBV+ malignant and benign conditions as well as in healthy carriers.MethodsOral secretions and blood cells from 31 children with IM, and biopsies from 14 EBV+ reactive lymphoid hyperplasia and 33 EBV+ lymphomas were included. LMP1 was amplified by nested PCR and sequenced. Phylogenetic reconstructions were made under Maximun Likelihood, Bayesian and coalescent algorithms.ResultsSix clades were defined (China1, China2, Med-, Alaskan, B95.8 and Argentine). Argentine variants, the most prevalent (46%), harbored 3 distinctive mutations and were a recombination between Raji and China1. Despite no pathology or compartment associations were observed for LMP1, the Argentine clade showed a phylogeographic association with our region. LMP1 estimated evolution rate was 8.591x10-5s/s/y and the estimated tMRCA for Raji and Argentine was 136ybp.ConclusionsAn LMP1 Argentine clade was defined. LMP1 evolutionary rate was higher than expected for herpesviruses. The tMRCA for Raji and the Argentine agrees with African immigration and could explain the recombinant nature of the Argentine variant.

Highlights

The Epstein Barr Virus (EBV), a member of the Herpesviridae family, was the first gammaherpervirus to be identified [1] and the first human virus assumed to be oncogenic [2]
EBV is related to various tumors in humans, including Hodgkin lymphoma (HL), Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC), gastric carcinoma, T-cell lymphoma and lymphoproliferative disorders in immunocompromised individuals (PTLD)
Since isolate IM31 is identical to Raji, but contains the mentioned mutations, these results suggest that IM31 could be a parental sequence for the predominant clade isolates

Summary

Introduction

The Epstein Barr Virus (EBV), a member of the Herpesviridae family, was the first gammaherpervirus to be identified [1] and the first human virus assumed to be oncogenic [2]. Primary infection most commonly occurs during childhood, as the case of Argentina. Under this scenario, primary EBV infection takes place a few years after birth and seroconversion is almost universal by the age of 6 years. Primary EBV infection is usually asymptomatic but, in some cases, may develop into a mild case of infectious mononucleosis (IM) [3,4]. In developed regions or high socio-economic groups, less than 40% of the population becomes infected with EBV during childhood; when primary infection is delayed until adolescence or early adulthood, it usually develops into a more severe case of IM [5]. EBV is related to various tumors in humans, including Hodgkin lymphoma (HL), Burkitt lymphoma (BL), nasopharyngeal carcinoma (NPC), gastric carcinoma, T-cell lymphoma and lymphoproliferative disorders in immunocompromised individuals (PTLD)

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