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Sequence variation of the Epstein-Barr virus nuclear antigen 1 (EBNA1) gene in chronic lymphocytic leukemia and healthy volunteer subjects

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Abstract

Epstein-Barr virus–related malignancies have been linked to variations in the sequences of EBV genes, notably EBNA1. Therefore, the purpose of this study was to examine the DBD/DD domain and USP7 binding domain sequences at the C-terminus of the EBNA1 gene in patients with chronic lymphocytic leukemia (CLL). This study included 40 CLL patients and 21 healthy volunteers. Using commercial kits, total DNA was extracted from buffy coat samples, and each sample was tested for the presence of the EBV genome. The C-terminus of EBNA1 was then amplified from positive samples, using nested PCR. Sanger sequencing was used to identify mutations in the PCR products, and the results were analyzed using MEGA11 software. The mean ages of CLL patients and healthy individuals were 61.07 ± 10.2 and 59.08 ± 10.3, respectively. In the EBNA-1 amplicons from CLL patients and healthy individuals, 38.5% and 16.7%, respectively, harbored mutations in the DBD/DD domain of the C-terminal region of the EBNA1 gene (P = 0.378). The mutation frequency at locus 97,320 was significantly higher in CLL patients than in healthy individuals (P = 0.039). Three EBV subtypes based on residue 487 were detected. The frequency of alanine, threonine, and valine in both groups was 88, 8, and 4 percent, respectively (P = 0.207). Moreover, all of the isolates from healthy donors had alanine at this position. The findings indicated that the presence of threonine or valine at residue 487 as well as a synonymous substitution at residue 553 in the C-terminal region of EBNA1 might be involved in the pathogenesis of EBV in CLL patients.

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Data Availability

The datasets analyzed in the current study are available from the corresponding author on reasonable request.

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Acknowledgments

The present study was extracted from a thesis written by Zahra Vafapour, which was financially supported by a grant from Shiraz University of Medical Sciences (no. 22644).

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Authors and Affiliations

  1. Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, P.O. Box: 71345-1735, Shiraz, Iran

    Zahra Vafapour, Fatemeh Hosseini Tabatabaie, Seyed Younes Hosseini, Seyed Mohammad Ali Hashemi, Afagh Moattari & Jamal Sarvari

  2. Department of Hematology and Medical Oncology, Shiraz University of Medical Sciences, Shiraz, Iran

    Shirin Haghighat

  3. Gastroenterohepatology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Jamal Sarvari

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  1. Zahra Vafapour
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  2. Fatemeh Hosseini Tabatabaie
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  5. Seyed Mohammad Ali Hashemi
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Contributions

Study concept: Sarvari J. Bench work: Vafapour Z, Hosseini Tabatabaie F, and Hashemi SMA. Data analysis: Sarvari J, Vafapour Z, Hosseini Tabatabaie F, and Hosseini SY. Manuscript drafting: Vafapour Z, Sarvari J, Hosseini SY, Haghighat S, and Moattari A. Critical revision of the manuscript: Hosseini SY, Sarvari J, Haghighat S, and Moattari A. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jamal Sarvari.

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Ethical approval

The study was approved by Ethics Committee of Shiraz University of Medical Sciences (IR.SUMS.REC.1400.377).

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Informed consent was obtained from all subjects involved in the study.

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The authors declare no conflict of interest.

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Communicated by Graciela Andrei

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Vafapour, Z., Tabatabaie, F., Hosseini, S. et al. Sequence variation of the Epstein-Barr virus nuclear antigen 1 (EBNA1) gene in chronic lymphocytic leukemia and healthy volunteer subjects. Arch Virol 169, 1 (2024). https://doi.org/10.1007/s00705-023-05933-0

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