Analysis of EBNA-1 and LMP-1 variants in diseases associated with EBV infection in Chinese children

Abstract

BackgroundIn China, primary EBV infection occurs during childhood with seroprevalence reaching about 100% by 10 years of age. There are few studies on EBV variants in diseases associated with EBV infection in Chinese children. In this study, we investigated the diversity of the EBV genes (EBNA-1 and LMP-1) and the relationship between EBV variants and the clinical phenotypes in diseases associated with EBV infections in Chinese pediatric cases.ResultsThe frequencies of EBV type I in the IM, HLH and HL samples were 98.4%, 100% and 95.8%, respectively. Three known EBNA-1 variants were identified, including V-val (all were V-val-v1 sub-variant), P-thr' and V-Leu (MT). The frequency of V-val-v1 was 98.6% in the IM samples, 100% in the HLH samples and 97.1% in the HL samples. There were no significant differences of the distribution of EBNA-1 variants between IM, HLH and HL samples (P > 0.05). Three known LMP-1 variants, including China 1, China 2 and Med, were identified and China 1 was predominant in all groups (IM 88.6%, HLH 100% and HL 100%). The frequency of del-LMP-1 was 88.6% in the IM samples, 100% in the HLH samples and 96.0% in the HL samples. There were no significant differences in the frequency of del-LMP-1 between the IM, HLH and HL samples (P > 0.05). The frequency of XhoI loss was 90.6% in the IM samples, 100% in the HLH samples and 100% in the HL samples, with no significant difference in frequency (P > 0.05). In the EBV type I strain, V-val-v1 variant (EBNA-1) was linked with China1 variant (LMP-1) in 88.9% of the IM samples, 100% of the HLH samples and 80.0% of the HL samples in this study.ConclusionsType I EBV was the most prevalent subtype EBV in Chinese pediatric cases and V-val-v1 (EBNA-1) and China1 (LMP-1) variants were the most dominant variants. There was a strong linkage between V-val-v1 (EBNA-1) variant and China1 (LMP-1) variant in type I EBV. The sequence variation in EBV genes may represent a geographic polymorphism since no preferential associations were found between specific EBV variants and specific diseases in this study.

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

“…On the other hand, co-infection with several EBV variants was reported in adult patients with IM [46–48], probably given by a higher viral inoculum transmitted through kissing; however, in pediatric primary infection these co-infections are infrequent, as observed in our previous reports in other EBV genes [38,42,49] and by others [43,44]. Indeed, when studying chronic active EBV infection in children, Jin et al found a small proportion of co-infections but failed to do so in IM samples [44].…”

Epstein–Barr virus strains and variations: Geographic or disease‐specific variants?

“…The most frequent LMP1 variation is a 30 bp deletion (del‐LMP1) in the C‐terminus first detected in NPC patients from Southern China [Miller et al, ; Ai et al, ]. Nevertheless, several other authors have described the presence of this variation in other EBV‐associated malignancies while led to an increasing number of studies regarding the association with tumor development.…”

“…In fact, there are several hypotheses to explain the tumorigenicity of this variation [Mainou and Raab‐Traub, ]. The 30 bp deletion (168256–168287) results in the loss of 10 amino acid (codons 346–355), which are involved in the transformation effector site 2 (TES2) (codons 352–386), leading to a more oncogenic variant [Tao et al, ; Zhang et al, ; Chang et al, ; Ai et al, ]. In vitro, studies revealed that the del‐LMP1 has the capacity to transform established rodent fibroblasts and immortalize human keratinocytes, allowing cells to escape immunosurveillance [Li et al, ; Zhang et al, ].…”

“…There have been several studies showing different sequence variations in other regions of LPM1 rather than C‐terminus [See et al, ]. The loss of XhoI restriction site in the exon 1 of the LMP1 gene, caused by a single base substitution from G to T at the nucleotide position 169425, was first described by Hu et al [] in the CAO cell line derived from a Chinese NPC case [Ai et al, ].…”

Epstein–Barr Virus Strain Variation

“…A subsequent report confirmed the subtypes but found no association with lymphoma (Habeshaw et al 1999). The variation might affect immune recognition of EBNA1 (Wrightham et al 1995;Chen et al 1999;Bell et al 2008) and has been noted in Chinese NPC samples (Ai et al 2012;Snudden et al 1995;Zhang et al 2004;Wang et al 2010a) and gastric cancer ), but there is no substantial evidence of disease association. It has been reported that the V-val subtype of EBNA1 has increased ability to activate the enhancer functions of oriP in transfection assays (Do et al 2008;Mai et al 2010).…”