Expression of HCMV-Encoded miR-UL148D and miR-UL36-3P in Women with HCMV-Associated Miscarriage: A Case-Control Study
Abstract
Objectives: To evaluate the expression levels of HCMV-encoded miR-UL148D and miR-UL36-3P in women with a miscarriage associated with HCMV infection.
Material and Methods: A case-control study was designed to include 50 women who had miscarriages due to active human cytomegalovirus (HCMV) infection, with a high HCMV viral load >10×10³ copies/mL, and a control group consisting of 50 healthy pregnant women who had not previously experienced miscarriages. RNAs were extracted from buffy coat samples to measure the HCMV-miR-UL148D and HCMV-miR-UL36-3P gene expression by the quantitative reverse transcription PCR (qRT-PCR) technique.
Results: Both HCMV-miR-UL148D and HCMV-miR-UL36-3P were significantly upregulated in miscarriage patients (2.66-fold and 21.16-fold changes, respectively; p-value<0.001). ROC analysis demonstrated strong diagnostic performance. For HCMV-miR-UL148D, sensitivity was 96%, and specificity was 98% (AUC=0.94). For HCMV-miR-UL36-3P, sensitivity was 91%, and specificity was 87% (AUC=0.94).
Conclusion: Elevated expressions of HCMV-encoded miR-UL148D and miR-UL36-3P may contribute to HCMV-associated miscarriage and could serve as potential biomarkers for adverse pregnancy outcomes.
Keywords
Full Text:
PDF (Early Version)References
Sijmons S, Van Ranst M, Maes P. Genomic and functional characteristics of human cytomegalovirus revealed by next-generation sequencing. Viruses 2014;6:1049-72. doi: 10.3390/v6031049.
Qader SM, Al-Azzawy MA, Tawfiq SK. Possible roles of human cytomegalovirus immunoglobulin G and its avidity to specific human cytomegalovirus antigens in the prevention of abortion among pregnant women. Med J Babylon 2023;20:S41-7. doi: 10.4103/MJBL.MJBL_368_22.
Wang C, Biddison LD, Arafat D, Chaudhury S, Zhao L, Kim H, et al. Congenital cytomegalovirus infection: recent advances in understanding viral transmission, pathogenesis, and potential intervention strategies. J Clin Med 2024;13:640. doi: 10.3390/jcm13020640.
Syggelou A, Iacovidou N, Kloudas S, Christoni Z, Papaevangelou V. Congenital cytomegalovirus infection. Ann N Y Acad Sci 2010;1205:144-7. doi: 10.1111/j.1749-6632.2010.05649.x.
Dupont L, Reeves MB. Cytomegalovirus latency and reactivation: recent insights into an age-old problem. Rev Med Virol 2016;26:75-89. doi: 10.1002/rmv.1862.
Nigro G, Muselli M, CCVC Group. Prevention of congenital cytomegalovirus infection: review and case series of valaciclovir versus hyperimmune globulin therapy. Viruses 2023;15:1376. doi: 10.3390/v15061376.
Nilsen TW. Mechanisms of microRNA-mediated gene regulation in animal cells. Trends Genet 2007;23:243-9.
Duca M. MicroRNAs as targets for small-molecule binders. In: RNA as a drug target: next frontiers in medicinal chemistry. 2024:119-50. doi: 10.1002/9783527840458.ch6.
Khikani AN, Firat M, Al-Khafaji ZA. Association of HCMV-miR-UL36-5P gene expression with miscarriages in women with human cytomegalovirus infection in Babylon, Iraq. Al-Rafidain J Med Sci 2024;7:43-8. doi: 10.54133/ajms.v7i2.1363.
SAS Institute Inc. Statistical analysis system (SAS), version 9: user’s guide. Cary (NC): SAS Institute Inc.; 2012.
Kim Y, Lee S, Kim S, Kim D, Ahn JH, Ahn K. Human cytomegalovirus clinical strain-specific microRNA miR-UL148D targets the human chemokine RANTES during infection. PLoS Pathog 2012;8:e1002577. doi: 10.1371/journal.ppat.1002577.
Pan Y, Zhang Y, Jia Y, et al. Circulating human cytomegalovirus-encoded HCMV-miR-US4-1 as an indicator for predicting the efficacy of IFNα treatment in chronic hepatitis B patients. Sci Rep 2016;6:23007. doi: 10.1038/srep23007.
Ding M, Wang X, Wang Y, et al. Distinct expression profile of HCMV-encoded miRNAs in plasma from oral lichen planus patients. J Transl Med 2017;15:198. doi: 10.1186/s12967-017-1222-8.
Barbu MG, Condrat CE, Thompson DC, Bugnar OL, Cretoiu D, Toader OD, et al. MicroRNA involvement in signaling pathways during viral infection. Front Cell Dev Biol 2020;8:143. doi: 10.3389/fcell.2020.00143.
Babu SG, Pandey M, Shanmugam G, et al. Role of HCMV miR-UL70-3p and miR-UL148D in overcoming cellular apoptosis. Mol Cell Biochem 2014;393:89-98. doi: 10.1007/s11010-014-2049-8.
Pan C, Zhu D, Wang Y, et al. Human cytomegalovirus miR-UL148D facilitates latent viral infection by targeting host cell immediate early response gene 5. PLoS Pathog 2016;12:e1006007. doi: 10.1371/journal.ppat.1006007.
Diggins NL, Hancock MH. HCMV miRNA targets reveal important cellular pathways for viral replication, latency, and reactivation. Noncoding RNA 2018;4:29. doi: 10.3390/ncrna4040029.
Cheng S, Caviness K, Buehler J, et al. Transcriptome-wide characterization of human cytomegalovirus in natural infection and experimental latency. Proc Natl Acad Sci USA 2017;114:E10586-95. doi: 10.1073/pnas.17105221.
Lau B, Poole E, Krishna B, et al. Human cytomegalovirus miR-UL112-1 promotes down-regulation of viral immediate early gene expression during latency to prevent T-cell recognition of latently infected cells. J Gen Virol 2016;97:2387-98. doi: 10.1099/jgv.0.000546.
Gao Z, Zhou L, Bai J, Ding M, Liu D, Zheng S, et al. Assessment of HCMV-encoded microRNAs in plasma as potential biomarkers in pregnant women with adverse pregnancy outcomes. Ann Transl Med 2021;9:638. doi: 10.21037/atm-20-7354.
Zhou W, Li X, Wang X, et al. Different expression pattern of human cytomegalovirus-encoded microRNAs in circulation from virus latency to reactivation. J Transl Med 2020;18:1-13. doi: 10.1186/s12967-020-02653-w.
Al-Muswie RT, Enayah SH, Ghaleb RA. Synergistic effects of Cassia fistula extract combination with cisplatin on the regulation of microRNA-145 and gene expression in colon cancer cell line SW480. Med J Babylon 2023;20:670-80. doi: 10.4103/MJBL.MJBL_33_23.
Al-Khafaji ZAI, Firat M, Shndiwe AN. Evaluation of up-regulated miR-UL22A-3p gene expression in miscarriages women infected with human cytomegalovirus as biomarker for pregnancy complications. Microb Biosyst 2025;10:322165. doi: 10.21608/mb.2024.322165.1171.
Huang Y, Qi Y, Ma Y, et al. Down-regulation of human cytomegalovirus UL138, a novel latency-associated determinant, by HCMV-miR-UL36. J Biosci 2013;38:479-85. doi: 10.1007/s12038-013-9353-4.
Kim S, Lee S, Shin H, et al. Temporal landscape of microRNA-mediated host-virus crosstalk during productive human cytomegalovirus infection. Cell Host Microbe 2015;17:838-51. doi: 10.1016/j.chom.2015.05.014.
Golshan M, Yaghobi R, Geramizadeh B, Afshari A, Shahroodi JR, Malek-Hosseini SA. Determination of the importance of miR-UL148D gene expression pattern in cytomegalovirus infected transplant patients. Int J Org Transplant Med 2021;12:54.
Refbacks
- There are currently no refbacks.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.