The impact of Epstein-Barr Virus genomic variations on clinical subtypes and prognosis in EBV-associated diseases

Objective Epstein-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 EBV across different subtypes of EBV-associated diseases to investigate the impact of EBV mutations on disease progression and clinical outcomes. Methods A total of 36 patients with EBV-associated diseases were enrolled. Peripheral blood DNA samples (400µL) were collected and sequenced using Illumina sequencing technology. Following quality control with FastQC, Fastp, and TriTrimmomatic, 27 samples meeting the critera of minimum effective coverage > 10 and coverage > 80% were retained. Single nucleotide polymorphisms (SNP) annotations were generated into VCF files, and mutation profiles were visualized using heatmaps. Mutational 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. Results Compared with the reference stain B95.8, a total of 2182 mutation sites were identified in 27 samples. The mutations located in coding region included 523 missense variants, 1 insertion mutations, and 2 deletion mutations, all of which only involved single amino acid changes in the encoded proteins. Although a large number of mutations were detected, no statistically significant differences were observed among the IM, CAEBV and lymphoma groups, or between patients with and without HLH. However, three mutation sites 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)]. Conclusion Single amino acid changes in EBV proteins had no significant effect on the progression status of EBV-associated diseases, but the mutation in BFLF1 were associated with an increased risk of mortality.