Altered serum human cytomegalovirus microRNA levels are common and closely associated with the inflammatory status in patients with fever

被引:1
作者
Wang, Cheng [1 ,2 ]
Zhu, Yunhua [1 ,2 ]
Chen, Penglu [1 ,2 ]
Wang, Chen [2 ]
Zhou, Wanqing [1 ,2 ]
Zhang, Cuiping [1 ]
Wang, Jing [1 ]
Chen, Xi [2 ]
Ding, Meng [1 ,2 ]
Zhang, Chunni [1 ,2 ]
Wang, Jun-Jun [1 ]
Zhang, Chen-Yu [1 ,2 ]
机构
[1] Nanjing Univ, Jinling Hosp, NJU Adv Inst Life Sci NAILS, Sch Life Sci,Dept Clin Lab,State Key Lab Pharmaceu, Nanjing, Peoples R China
[2] Nanjing Univ, Sch Life Sci, Inst Artificial Intelligence Biomed, Nanjing Drum Tower Hosp Ctr Mol Diagnost & Therapy, Nanjing, Peoples R China
来源
FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷
基金
中国国家自然科学基金;
关键词
HCMV; human cytomegalovirus; serum; fever; risk factor; immune disorders; microRNA; UNKNOWN ORIGIN; EXPRESSION; DIAGNOSIS; PROFILE; TURKEY;
D O I
10.3389/fimmu.2022.1079259
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
BackgroundFever has a complicated etiology, and diagnosing its causative factor is clinically challenging. Human cytomegalovirus (HCMV) infection causes various diseases. However, the clinical relevance, prevalence, and significance of HCMV microRNAs (miRNA) in association with fever remain unclear. In the present study, we analyzed the HCMV miRNA expression pattern in the serum of patients with fever and evaluate its clinical associations with occult HCMV infection status in immune disorders. MethodsWe included serum samples from 138 patients with fever and 151 age-gender-matched controls in this study. First, the serum levels of 24 HCMV miRNAs were determined using a hydrolysis probe-based stem-loop quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay in the training set. The markedly altered miRNAs were verified in the validation and testing sets. The serum HCMV IgG/IgM and DNA titers in the testing cohort were also assessed using enzyme-linked immunosorbent assay (ELISA) and RT-qPCR, respectively. ResultsThe majority of HCMV miRNAs were markedly upregulated in the serum of fever patients. We selected the five most significantly altered HCMV miRNAs: hcmv-miR-US4-3p, hcmv-miR-US29-3p, hcmv-miR-US5-2-3p, hcmv-miR-UL112-3p, and hcmv-miR-US33-3p for validation. These miRNAs were also significantly elevated in the serum of fever patients in the validation and testing sets compared with the controls. Logistic regression analysis revealed that the five miRNAs were novel potential risk factors for fever. Notably, the serum levels of four of the five confirmed HCMV miRNAs were significantly associated with blood C-reaction protein concentrations. Moreover, the five HCMV miRNA levels were closely correlated with the HCMV DNA titers in the testing cohort. ConclusionHCMV infection and activation are common in fever patients and could be novel risk factors for fever. These differentially expressed HCMV miRNAs could enable HCMV activation status monitoring in immune disorders.
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页数:14
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