Evolutionary dynamics of genetic variation in Epstein-Barr virus isolates of diverse geographical origins: evidence for immune pressure-independent genetic drift.

Epstein–Barr virus (EBV) is associated with several malignancies. Specific EBV gene variants, e.g. the BamHI f configuration, a C-terminal region 30 bp deletion in the latent membrane protein-1 (LMP1) gene (del-LMP) and the loss of an XhoI site in LMP1 (XhoI-loss), are found in Chinese cases of nasopharyngeal carcinoma (NPC), suggesting that EBV sequence variation may be involved in oncogenesis. In order to understand better the epidemiology of these EBV variants, they were studied in virus isolates from EBV-positive Chinese cases of Hodgkin’s disease (HD; n=71) and donor throat washings from healthy Chinese. Sequencing was performed of 15 representative EBV isolates, including the first analysis of the LMP1 promoter in Asian wild-type EBV isolates. The following observations were made. (i) Three EBV LMP1 variants were identified, designated Chinese groups (CG) 1–3. In both EBV-associated HD and in healthy Chinese, CG1-like viruses showing del-LMP1 and XhoI-loss were predominant. (ii) CG1viruses were distinct from European and African variants, suggesting that this profile is useful for epidemiological studies. (iii) Specific patterns of mutations were present in the LMP1 promoter in both CG1 and CG2. (iv) The BamHI f variant was not found in Chinese HD, in contrast to Chinese NPC and European HD. This study confirms that EBV isolates in Chinese HD and other tumours differ from those reported in Western cases. However, this reflects the predominant virus strain present in the healthy Chinese population, suggesting that these are geographically restricted polymorphisms rather than tumour-specific strains.

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Unexpected Absence of the Epstein-Barr Virus (EBV) lyLMP-1 Open Reading Frame in Tumor Virus Isolates: Lack of Correlation between Met129 Status and EBV Strain Identity

Journal of Virology ◽

10.1128/jvi.77.7.4415-4422.2003 ◽

2003 ◽

Vol 77 (7) ◽

pp. 4415-4422 ◽

Cited By ~ 9

Author(s):

Kimberly D. Erickson ◽

Christoph Berger ◽

William F. Coffin ◽

Edwin Schiff ◽

Dennis M. Walling ◽

...

Keyword(s):

Cell Lines ◽

Epstein Barr Virus ◽

Open Reading Frame ◽

Lytic Cycle ◽

Reading Frame ◽

Barr Virus ◽

Tumor Virus ◽

Epstein Barr ◽

Virus Isolates ◽

Codon 129

ABSTRACT The lytic cycle-associated lytic latent membrane protein-1 (lyLMP-1) of Epstein-Barr virus (EBV) is an amino-terminally truncated form of the oncogenic LMP-1. Although lyLMP-1 shares none of LMP-1's transforming and signal transducing activities, we recently reported that lyLMP-1 can negatively regulate LMP-1-stimulated NF-κB activation. The lyLMP-1 protein encoded by the B95-8 strain of EBV initiates from methionine 129 (Met129) of the LMP-1 open reading frame (ORF). The recent report that Met129 in the B95-8 LMP-1 ORF is not conserved in the Akata strain of EBV prompted us to screen a panel of EBV-positive cell lines for conservation of Met129 and lyLMP-1 expression. We found that 15 out of 16 tumor-associated virus isolates sequenced encoded an ATT or ACC codon in place of ATG in the LMP-1 ORF at position 129, and tumor cell lines harboring isolates lacking an ATG at codon 129 did not express the lyLMP-1 protein. In contrast, we found that EBV DNA from 22 out of 37 healthy seropositive donors retained the Met129 codon. Finally, the lyLMP-1 initiator occurs variably within distinct EBV strains and its presence cannot be predicted by EBV strain identity. Thus, Met129 is not peculiar to the B95-8 strain of EBV, but rather can be found in the background of several evolutionarily distinct EBV strains. Its absence from EBV isolates from tumors raises the possibility of selective pressure on Met129 in EBV-dependent tumors.

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Difference of Epstein–Barr virus isolates from Japanese patients and African Burkitt’s lymphoma cell lines based on the sequence of latent membrane protein 1

Virus Genes ◽

10.1007/s11262-006-0010-y ◽

2007 ◽

Vol 34 (1) ◽

pp. 55-61 ◽

Cited By ~ 11

Author(s):

Kyosuke Kanai ◽

Yukio Satoh ◽

Yuriko Saiki ◽

Haruo Ohtani ◽

Takeshi Sairenji

Keyword(s):

Membrane Protein ◽

Cell Lines ◽

Epstein Barr Virus ◽

Japanese Patients ◽

Latent Membrane Protein ◽

Lymphoma Cell ◽

Latent Membrane Protein 1 ◽

Barr Virus ◽

Epstein Barr ◽

Virus Isolates

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Differential Regulation of Epstein-Barr Virus (EBV) Latent Gene Expression in Burkitt Lymphoma Cells Infected with a Recombinant EBV Strain

Journal of Virology ◽

10.1128/jvi.75.10.4929-4935.2001 ◽

2001 ◽

Vol 75 (10) ◽

pp. 4929-4935 ◽

Cited By ~ 16

Author(s):

Pankaj Trivedi ◽

Paola Spinsanti ◽

Laura Cuomo ◽

Massimo Volpe ◽

Kenzo Takada ◽

...

Keyword(s):

Epstein Barr Virus ◽

Differential Regulation ◽

Type I ◽

Phenotypic Differences ◽

Barr Virus ◽

Immune Pressure ◽

Restricted Type ◽

Promoter Usage ◽

Epstein Barr

ABSTRACT Epstein-Barr virus (EBV)-negative Burkitt lymphomas (BLs) can be infected in vitro with prototype EBV strains to study how the virus may affect the phenotype of tumor cells. Studies thus far have concentrated on the use of transforming B95-8 and nontransforming P3HR1 strains. Immunological and phenotypic differences between the sublines infected with these two strains were reported. The majority of these differences, if not all, can be attributed to the lack of EBNA-2 coding sequences in the P3HR1 strain. The recent development of a selectable Akata strain has opened up new possibilities for infecting epithelial and T cells as well. We infected five EBV-negative BL lines with the recombinant Akata virus. Our results indicate that the infected cell lines BL28, Ramos, and DG75 express EBNA-1, EBNA-2, and LMP1, the viral proteins associated with type III latency, and use both YUK and QUK splices. In contrast, two EBV-negative variants of Akata and Mutu when reinfected displayed restricted type I latency and expressed only EBNA-1. All clones of infected Mutu cells used the QUK splice exclusively. The usage of Qp was observed in a majority of Akata clones. Some Akata clones, however, were found to have double promoter usage (Qp and C/Wp) but at 4 months after infection did not express EBNA-2. The results demonstrate differential regulation of EBV latency in BLs with the same recombinant viral strain and suggest that the choice of latency type may be cell dependent. The restricted latency observed for infected Akata and Mutu cells indicates that a BL may opt for type I latency in the absence of immune pressure as well.

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