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Human microRNA responses predict cytomegalovirus replication following solid organ transplantation


Han, Sang Hoon; Kumar, D; Ferreira, V H; Egli, A; Hirsch, H H; Weisser, M; Garzoni, C; van Delden, C; Bochud, P Y; Manuel, O; Meylan, P; Boggian, K; Husain, S; Mueller, N J; Humar, A; Swiss Transplant Cohort Study (2017). Human microRNA responses predict cytomegalovirus replication following solid organ transplantation. Journal of Infectious Diseases, 215(4):537-546.

Abstract

BACKGROUND: Homo sapiens mature microRNA-200b-3p and -200c-3p are predicted to bind to 3' UTR of mRNA encoding human cytomegalovirus (HCMV) immediate early protein 2 (IE2). We hypothesized that expression of these microRNAs pre-transplant could predict HCMV replication after solid organ transplantation (SOT).
METHODS: 272 SOT recipients were HCMV-seropositive pre-transplant and were managed using pre-emptive therapy. Pre-transplant PBMCs were stimulated with HCMV followed by collection of RNA one day post-stimulation. MicroRNAs were quantified using real-time RT-PCR. Human foreskin fibroblasts were transfected with 200b-3p and 200c-3p and infected with HCMV one hour post-transfection. Protein was collected at 3- and 7-dpi and 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 (OR: 0.53, P = .02), D-/R+ HCMV serostatus (OR: 0.55, P = .02) and graft rejection (OR: 1.86, P = .03) were independently associated with HCMV replication. Transfection with 200b-3p resulted in 2.7- and 2.5-fold decreased IE2 at 3- and 7-dpi, respectively, compared to mock cells.
CONCLUSIONS: MicroRNAs may play a biologically relevant role in controlling HCMV replication post-transplant.

Abstract

BACKGROUND: Homo sapiens mature microRNA-200b-3p and -200c-3p are predicted to bind to 3' UTR of mRNA encoding human cytomegalovirus (HCMV) immediate early protein 2 (IE2). We hypothesized that expression of these microRNAs pre-transplant could predict HCMV replication after solid organ transplantation (SOT).
METHODS: 272 SOT recipients were HCMV-seropositive pre-transplant and were managed using pre-emptive therapy. Pre-transplant PBMCs were stimulated with HCMV followed by collection of RNA one day post-stimulation. MicroRNAs were quantified using real-time RT-PCR. Human foreskin fibroblasts were transfected with 200b-3p and 200c-3p and infected with HCMV one hour post-transfection. Protein was collected at 3- and 7-dpi and 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 (OR: 0.53, P = .02), D-/R+ HCMV serostatus (OR: 0.55, P = .02) and graft rejection (OR: 1.86, P = .03) were independently associated with HCMV replication. Transfection with 200b-3p resulted in 2.7- and 2.5-fold decreased IE2 at 3- and 7-dpi, respectively, compared to mock cells.
CONCLUSIONS: MicroRNAs may play a biologically relevant role in controlling HCMV replication post-transplant.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:15 February 2017
Deposited On:26 Jan 2017 10:17
Last Modified:20 Apr 2017 01:02
Publisher:Oxford University Press
ISSN:0022-1899
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/infdis/jiw596
PubMed ID:28003351

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