ArticleHereditas2026
BFLF1 gene polymorphisms are associated with increased mortality in patients with EBV-associated diseases.
Article in Hereditas, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectiveEpstein-Barr virus (EBV) -associated diseases comprise a spectrum of conditions, including infectious mononucleosis (IM) and chronic active EBV infections (CAEBV), as well as malignant lymphomas. The study aimed to compare genomic variations of Type 1 EBV across different subtypes of EBV-associated diseases to investigate the impact of EBV variants on disease progression and clinical outcomes.
methodsA total of 36 patients with EBV-associated diseases were enrolled. Targeted EBV genome sequencing on EBV genomic was performed with peripheral blood DNA samples (400µL) using Illumina sequencing technology. Following quality control with FastQC, Fastp, and TriTrimmomatic, 27 samples comprising 2 IM, 9 CAEBV and 16 NK/T-cell lymphoma cases meeting the critera of minimum effective coverage > 10 and coverage > 80% were retained. Single nucleotide polymorphisms (SNP) annotations were generated into VCF files, and variant profiles were visualized using heatmaps. Variant rates were compared using Fisher's exact test, based on disease subtype, presence of hemophagocytic lymphohistiocystosis (HLH), and clinical outcomes. Odds ratios (ORs) were calculated using the Haldane-Anscombe correction.
resultsCompared with the reference stain B95.8/Raji, a total of 2182 variants were identified in 27 samples. The variants located in coding region included 523 missense variants, 1 insertion, and 2 deletion, all of which only involved single amino acid changes in the encoded proteins. Although a large number of variants were detected, no statistically significant differences were observed among the IM, CAEBV and lymphoma groups, or between patients with and without HLH. However, three variants in BFLF1 were significantly more frequent in deceased patients compared to survivors, which detailedly refers to Ile35Thr, Asp44Glu and Val246Ile [P = 0.0267, OR = 15.00, 95%CI= (0.7436,301.5)].
conclusionSingle amino acid changes in EBV proteins had no significant effect on the progression status of EBV-associated diseases, but the variants in BFLF1 were associated with an increased risk of mortality.
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