Novel plasma microRNA expression features in diagnostic use for Epstein-Barr virus-associated febrile diseases

YiFei Xu; Ying Chen; Qingluan Yang; Yuxiang Lu; Rui Zhou; Haohua Liu; Yanjie Tu; Lingyun Shao

doi:10.1016/j.heliyon.2024.e26810

Novel plasma microRNA expression features in diagnostic use for Epstein-Barr virus-associated febrile diseases

Heliyon. 2024 Feb 23;10(5):e26810. doi: 10.1016/j.heliyon.2024.e26810. eCollection 2024 Mar 15.

Authors

YiFei Xu¹, Ying Chen¹, Qingluan Yang², Yuxiang Lu¹, Rui Zhou¹, Haohua Liu¹, Yanjie Tu^{1

3}, Lingyun Shao²

Affiliations

¹ School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.
² Department of Infectious Diseases, National Medical Center for InfectiousDiseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety EmergencyResponse, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, People's Republic of China.
³ Department of Febrile Disease, School of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People's Republic of China.

Abstract

Background: Epstein-Barr virus (EBV) is widely infected in humans and causes various diseases. Among them, microRNAs of EBV play a key role in the progression of EBV-associated febrile diseases. There're few specific indicators for rapid differential diagnosis of various febrile diseases associated with EBV, and the lack of more reliable screening methods with high diagnostic utility has led to spaces for improvement in the accurate diagnosis and efficient treatment of relevant patients, making EBV infection a complicated clinical problem. With recent advances in plasma microRNA testing, the apparent presence of EBV microRNAs in plasma can help screen for EBV infection. The gene networks targeted by these microRNAs can also indicate potential biomarkers of EBV-associated febrile diseases. This study aimed to identify some novel miRNAs as potential biomarkers for early diagnosis of respectively EBV-associated febrile diseases.

Materials and methods: A total of 110 participants were recruited for this task. First, we performed high-throughput sequencing and preliminary PCR validation of differentially expressed miRNAs in 15 participants with EBV-associated fever (divided into common EBV carriers), infectious mononucleosis (IM) and chronic active EBV infection (CAEBV), EBV-associated Hemophagocytic Lymphohistiocytosis group (EBV-HLH), and 3 healthy individuals. After a comprehensive analysis, 10 miRNAs with abnormal expression were screened, and then qRT-PCR was performed in the rest of 95 participants to detect the validation of miRNAs expression in plasma samples. Thereafter, we further investigated their potential for clinical application in EBV-related febrile diseases by using a combination of Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and Protein-protein interaction network analysis.

Results: Through identification and detailed analysis of the obtained data, we found significant differences in the expression of Hsa-miR-320d, EBV-miR-BART22, and EBV-miR-BART2-3p in blood samples from patients with different EBV-related febrile diseases. We found that the expression levels of Hsa-miR-320d, EBV-miR-BART22, and EBV-miR-BART2-3p in plasma are indicative of determining different disease types of EBV-related febrile diseases, while EBV-miR-BART22 and EBV-miR-BART2-3p may be potential therapeutic targets.

Conclusion: The expression levels of Hsa-miR-320d, EBV-miR-BART22, and EBV-miR-BART2-3p suggest that they may be used as transcriptional features for early differential diagnosis of EBV-related febrile diseases, and EBV-miR-BART22 and EBV-miR-BART2-3p may be potential therapeutic targets.

Keywords: EBV; EBV-HLH; Immune response; Molecular diagnostics; miRNA.