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- Title
Human MicroRNA Responses Predict Cytomegalovirus Replication Following Solid Organ Transplantation.
- Authors
Sang Hoon Han; Kumar, Deepali; Ferreira, Victor H.; Egli, Adrian; Hirsch, Hans H.; Weisser, Maja; Garzoni, Christian; van Delden, Christian; Bochud, Pierre-Yves; Manuel, Oriol; Meylan, Pascal; Boggian, Katia; Husain, Shahid; Mueller, Nicolas J.; Humar, Atul; Han, Sang Hoon; Kumar, D; Ferreira, V H; Egli, A; Hirsch, H H
- Abstract
<bold>Background: </bold>Homo sapiens mature micro-ribonucleic acid (miRNA)-200b-3p and 200c-3p are predicted to bind to 3' untranslated region of mRNA encoding human cytomegalovirus (HCMV) immediate early protein 2 (IE2). We hypothesized that expression of these miRNAs pretransplant could predict HCMV replication after solid organ transplantation (SOT).<bold>Methods: </bold>A total of 272 SOT recipients were HCMV-seropositive pretransplant and were managed using preemptive therapy. Pretransplant peripheral blood mononuclear cells were stimulated with HCMV followed by collection of RNA 1 day poststimulation. The miRNAs were quantified using real-time reverse transcription-polymerase chain reaction. Human foreskin fibroblasts were transfected with 200b-3p and 200c-3p and infected with HCMV 1 hour post-transfection. Protein was collected at 3 days postinfection (dpi) and 7 dpi underwent immunoblotting for IE2.<bold>Results: </bold>Medians of 200b-3p and 200c-3p were significantly lower in recipients with HCMV replication (n = 144) (361.6 vs 552.6, P = .035; 3586.8 vs 12986.8 copies/μL, P = .03, respectively). Multivariate regression revealed that 200b-3p ≥100 copies/μL (odds ratio [OR]: 0.53; P = .02), was associated with less HCMV replication. Transfection with 200b-3p resulted in 2.7- and 2.5-fold decreased IE2 at 3 dpi and 7 dpi, respectively, compared to mock cells.<bold>Conclusions: </bold>MicroRNAs may play a biologically relevant role in controlling HCMV replication post-transplant.
- Subjects
MICRORNA; CYTOMEGALOVIRUSES; TRANSPLANTATION of organs, tissues, etc.; MESSENGER RNA; GENE expression; HUMAN beings
- Publication
Journal of Infectious Diseases, 2017, Vol 215, Issue 4, p537
- ISSN
0022-1899
- Publication type
journal article
- DOI
10.1093/infdis/jiw596