title: Human MicroRNA Responses Predict Cytomegalovirus Replication Following Solid Organ Transplantation.
abstract: 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).
  
  
  
  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.
  
  
  
  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.
  
  
  
  MicroRNAs may play a biologically relevant role in controlling HCMV replication post-transplant.
authors.affiliation: Multi-Organ Transplant Program, University of Toronto, Ontario, Canada.|Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
authors.forename: Sang Hoon
authors.initials: SH
authors.lastname: Han
authors.affiliation: Multi-Organ Transplant Program, University of Toronto, Ontario, Canada.
authors.forename: Deepali
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Multi-Organ Transplant Program, University of Toronto, Ontario, Canada.
authors.forename: Victor H
authors.initials: VH
authors.lastname: Ferreira
authors.affiliation: Applied Microbiology Research, Department of Biomedicine, University of Basel, Switzerland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Egli
authors.affiliation: Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Switzerland.|Transplantation & Clinical Virology; Department Biomedicine, University of Basel, Switzerland.
authors.forename: Hans H
authors.initials: HH
authors.lastname: Hirsch
authors.affiliation: Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Switzerland.
authors.forename: Maja
authors.initials: M
authors.lastname: Weisser
authors.affiliation: Department of Internal Medicine and Infectious Diseases, Clinica Luganese, Lugano, Switzerland and Department of Infectious Diseases, Inselspital, Bern University Hospital and University of Bern, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Garzoni
authors.affiliation: Transplant Infectious Diseases Unit, University Hospitals Geneva, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: van Delden
authors.affiliation: Infectious Diseases Service, University Hospital and University of Lausanne, Switzerland.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Bochud
authors.affiliation: Infectious Diseases Service and Transplantation Center, University Hospital and University of Lausanne, Switzerland.
authors.forename: Oriol
authors.initials: O
authors.lastname: Manuel
authors.affiliation: Institute of Microbiology and Infectious Diseases Service, University Hospital and University of Lausanne, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Meylan
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, Switzerland.
authors.forename: Katia
authors.initials: K
authors.lastname: Boggian
authors.affiliation: Multi-Organ Transplant Program, University of Toronto, Ontario, Canada.
authors.forename: Shahid
authors.initials: S
authors.lastname: Husain
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland.
authors.forename: Nicolas J
authors.initials: NJ
authors.lastname: Mueller
authors.affiliation: Multi-Organ Transplant Program, University of Toronto, Ontario, Canada.
authors.forename: Atul
authors.initials: A
authors.lastname: Humar
mesh_terms: D000328:Adult; D000368:Aged; D002460:Cell Line; D003587:Cytomegalovirus / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000821:virology*; D005260:Female; D005500:Follow-Up Studies; D006367:HeLa Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D016015:Logistic Models; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D016377:Organ Transplantation; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D014779:Virus Replication
chemical_list: D017874:Immediate-Early Proteins; D035683:MicroRNAs; D012333:RNA, Messenger
keywords: cytomegalovirus; microRNA; solid organ transplant; immediate early protein