Sang Hoon Han1,2, Deepali Kumar1, Victor H Ferreira1, Adrian Egli3, Hans H Hirsch4,5, Maja Weisser4, Christian Garzoni6, Christian van Delden7, Pierre-Yves Bochud8, Oriol Manuel9, Pascal Meylan10, Katia Boggian11, Shahid Husain1, Nicolas J Mueller12, Atul Humar1. 1. Multi-Organ Transplant Program, University of Toronto, Ontario, Canada. 2. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. 3. Applied Microbiology Research, Department of Biomedicine, University of Basel, Switzerland. 4. Infectious Diseases & Hospital Epidemiology, University Hospital Basel, Switzerland. 5. Transplantation & Clinical Virology; Department Biomedicine, University of Basel, Switzerland. 6. 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. 7. Transplant Infectious Diseases Unit, University Hospitals Geneva, Switzerland. 8. Infectious Diseases Service, University Hospital and University of Lausanne, Switzerland. 9. Infectious Diseases Service and Transplantation Center, University Hospital and University of Lausanne, Switzerland. 10. Institute of Microbiology and Infectious Diseases Service, University Hospital and University of Lausanne, Switzerland. 11. Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, Switzerland. 12. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Switzerland.
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.
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.
Authors: Susanne Stampf; Nicolas J Mueller; Christian van Delden; Manuel Pascual; Oriol Manuel; Vanessa Banz; Isabelle Binet; Sabina De Geest; Pierre-Yves Bochud; Alexander Leichtle; Stefan Schaub; Jürg Steiger; Michael Koller Journal: BMJ Open Date: 2021-12-15 Impact factor: 2.692
Authors: Kyoung Hwa Lee; Beom Jin Lim; Victor H Ferreira; Seo Yeon Min; Yeon-Mi Hong; Jeong-Hyeon Jo; Sang Hoon Han Journal: Biosci Rep Date: 2018-12-07 Impact factor: 3.840