Publication

Human microRNA responses predict cytomegalovirus replication following solid organ transplantation

Journal Paper/Review - Dec 21, 2016

Units
PubMed
Doi

Citation
Han S, Humar A, Mueller N, Husain S, Boggian K, Meylan P, Manuel O, Bochud P, van Delden C, Garzoni C, Weisser M, Hirsch H, Egli A, Ferreira V, Kumar D. Human microRNA responses predict cytomegalovirus replication following solid organ transplantation. J Infect Dis 2016
Type
Journal Paper/Review (English)
Journal
J Infect Dis 2016
Publication Date
Dec 21, 2016
Issn Electronic
1537-6613
Brief description/objective

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.