Diversity of naturally occurring Epstein-Barr virus revealed by nucleotide sequence polymorphism in hypervariable domains in the BamHI K and N subgenomic regions.

Abstract

The extent of nucleotide sequence microheterogeneity varies among subgenomic regions of Epstein-Barr virus (EBV). We examined, in EBVcarrying lymphoid cell lines, the extent of polymorphism in EBV DNA fragments amplified from the BamHI E, K, N and Z regions, and then investigated the diversity of the more hypervariable regions in tissues and body fluids. In cell lines, sequence dissimilarities in a genotype-specifying fragment of the EBNA-3C gene varied from 1-4 % within each genotype ; dissimilarities in the first intron of the BZLF-1 gene were 2 % within each genotype. By contrast, dissimilarities in a C-terminal unique domain of the EBNA-1 gene, and in a fragment that encompasses and is upstream of the LMP-1 start codon, varied between 2 and 7 % and were not

Molecular profile of Epstein–Barr virus infection in HHV-8-positive primary effusion lymphoma

“…Large, multicentric studies comparing EBNA-1 sequences in PEL, as well as in immunodeficient and immunocompetent individuals without lymphoma, are required to conclusively define whether the EBNA-1 heterogeneity of PEL simply reflects geographical variations of EBV strains, as it has been proposed for other EBV positive lymphomas. [25][26][27][28] Independent of these observations, however, the high number of genotypes definable by EBNA-1 sequence variation provides a highly sensitive and specific marker for molecular epidemiology studies of EBV infection in PEL and for investigating intrahost EBV infection in these patients.…”

“…In fact, it has been proposed by some studies that Burkitt lymphoma may cluster with specific EBNA-1 variants, 22,23 although other investigators have questioned this hypothesis. [25][26][27][28] Because PEL fails to express the EBV transforming antigens LMP-1 and EBNA-2 and also fails to associate with specific EBNA-1 variants, the precise tumorigenic mechanism of EBV in the context of PEL remains to be defined.…”

“…[22][23][24] This hypothesis, however, has been recently questioned by other investigators. [25][26][27][28] On this basis, we screened a panel of PEL across several EBV loci. Our results indicate that: (1) individual PEL cases consistently harbor a single EBV strain; (2) EBNA-1 displays a high degree of heterogeneity in different PEL cases; (3) no specific EBV genotype preferentially associates with PEL.…”

“…The occurrence of P-thr subvariants in PEL is consistent with previous observations obtained from other human malignancies. [25][26][27][28] Finally, the EBNA-1 variant V-leu, was restricted to one single case of PEL (case 1911; Table 2 and Figure 2). In selected cases (n = 5), analysis of multiple subclones (n = 5) showed absence of intratumor heterogeneity of the EBNA-1 mutations.…”

“…[22][23][24] Subsequently, several other EBNA-1 variants have also been reported. [25][26][27][28] This study aimed at defining the distribution of EBNA-1 variants in PEL and at comparing it with the representation of EBNA-1 in non-neoplastic B cells from HIV-infected individuals. In order to further characterize the EBV genotype of PEL, several other molecular features of the virus were also investigated.…”