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Human MicroRNA Responses Predict Cytomegalovirus Replication Following Solid Organ Transplantation

Authors
 Sang Hoon Han  ;  Deepali Kumar  ;  Victor H. Ferreira  ;  Adrian Egli  ;  Hans H. Hirsch  ;  Maja Weisser  ;  Christian Garzoni  ;  Christian van Delden  ;  Pierre-Yves Bochud  ;  Oriol Manuel  ;  Pascal Meylan  ;  Katia Boggian  ;  Shahid Husain  ;  Nicolas J. Mueller  ;  Atul Humar  ;  Swiss Transplant Cohort Study 
Citation
 JOURNAL OF INFECTIOUS DISEASES, Vol.215(4) : 537-546, 2017 
Journal Title
 JOURNAL OF INFECTIOUS DISEASES 
ISSN
 0022-1899 
Issue Date
2017
MeSH
Adult ; Aged ; Cell Line ; Cytomegalovirus/physiology* ; Cytomegalovirus Infections/virology* ; Female ; Follow-Up Studies ; HeLa Cells ; Humans ; Immediate-Early Proteins/genetics ; Immediate-Early Proteins/metabolism ; Leukocytes, Mononuclear/metabolism ; Leukocytes, Mononuclear/virology ; Logistic Models ; Male ; MicroRNAs/genetics ; MicroRNAs/metabolism* ; Middle Aged ; Multivariate Analysis ; Organ Transplantation* ; Prospective Studies ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Reproducibility of Results ; Virus Replication*
Keywords
cytomegalovirus ; microRNA ; solid organ transplant ; immediate early protein
Abstract
BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: MicroRNAs may play a biologically relevant role in controlling HCMV replication post-transplant.
Full Text
https://academic.oup.com/jid/article-lookup/doi/10.1093/infdis/jiw596
DOI
10.1093/infdis/jiw596
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Han, Sang Hoon(한상훈) ORCID logo https://orcid.org/0000-0002-4278-5198
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154629
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