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

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.

Frequency of EBV LMP-1 Promoter and Coding Variations in Burkitt Lymphoma Samples in Africa and South America and Peripheral Blood in Uganda

“…Because our analysis suggests that Pattern B is predominant in people from the Far East, it is possible that the North Carolina strain also tracks with EBV from the Far East, although the finding that three Pattern B-North Carolina EBV samples were collected from individuals in Australia and an individual from Germany (all with unknown ancestry) suggests that this strain circulates elsewhere. The North Carolina strain was recently reported in about 12.2% of healthy donors from Qatar [ 35 ], but it was not found in a study of LMP-1 variants in the saliva and PBMCs in children in Argentina, who included people of Asian descent [ 36 ], suggesting that the North Carolina strain may not be specific for the EBV found in Far East populations. Taken together, our results provide a justification for conducting a secondary analysis of HTS data to evaluate LMP-1 variant-disease associations using these classifications.…”

Prevalence of salivary human herpesviruses in pediatric multiple sclerosis cases and controls

“…The high prevalence of low amplitude EBV in the adult cohorts suggests that mutations in this region of the virus are common. Indeed, lmp-1 is highly polymorphic, and lmp-1 nucleotide diversity has been used to define viral variants 34 .…”

A reliable Epstein-Barr Virus classification based on phylogenomic and population analyses

“…Other studies tried to classify this virus by geographic location sampling or according to single gene or small subset of EBV gene polymorphisms involved in certain pathologies 23,24 . Some classifications are based on variations of LMP-1 and EBNA-1 genes, for instance, one study analyzed part of the LMP-1 gene sequences to primarily establish 7 EBV strains 25,26 . However, after studying the complete LMP1 gene sequence, this classification was redefined into 6 EBV strains: Alaskan (AL), China1, China2, B95.8 (Med+), Med− and Argentine, indicating the impact of partial sequences to classify an organism 26,27 .…”