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Complexity of Host Micro-RNA Response to Cytomegalovirus Reactivation After Organ Transplantation

Egli, A, Lisboa, LF, O’Shea, D, Asberg, A, Mueller, T, Emery, VC, Kumar, D and Humar, H (2015) Complexity of Host Micro-RNA Response to Cytomegalovirus Reactivation After Organ Transplantation American Journal of Transplantation, 16. pp. 650-660.

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Abstract

Human (Homo sapiens)micro-RNAs (hsa-miRNAs) regulate virus and host-gene translation, but the biological impact in patientswith human cytomegalovirus (hCMV) infection is notwell defined in a clinically relevantmodel. First, we compared hsa-miRNA expression profiles in peripheral blood mononuclear cells from 35 transplant recipients with and without CMV viremia by using a microarray chip covering 847hsa-miRNAs. This approach demonstrated a set of 142 differentially expressed hsamiRNAs. Next, we examined the effect of each of these miRNAs on viral growth by using human fibroblasts (human foreskin fibroblast-1) infected with the hCMV Towne strain, identifyinga subset of proviral andantiviral hsa-miRNAs. miRNA-target prediction software indicated potential binding sites within the hCMV genome (e.g., hCMV-UL52 and -UL100 [UL¼unique long]) and host-genes (e.g., interleukin-1 receptor, IRF1). Luciferaseexpressing plasmid constructs and immunoblotting confirmed several predicted miRNA targets. Finally, we determined the expression of selected proviral and antiviral hsa-miRNAs in 242 transplant recipients with hCMV-viremia. We measured hsa-miRNAs before and after antiviral therapy and correlated hsa-miRNA expression levels to hCMV-replication dynamics. One of six antiviral hsa-miRNAs showed a significant increase during treatment, concurrent with viral decline. In contrast, six of eight proviral hsa-miRNAs showed a decrease during viral decline. Our results indicate that a complex and multitargeted hsa-miRNA response occurs during CMV replication in immunosuppressed patients. This study provides mechanistic insight and potential novel biomarkers for CMV replication.

Item Type: Article
Subjects : Microbial and Cellular Sciences
Divisions : Faculty of Health and Medical Sciences > School of Biosciences and Medicine > Department of Microbial and Cellular Sciences
Authors :
NameEmailORCID
Egli, AUNSPECIFIEDUNSPECIFIED
Lisboa, LFUNSPECIFIEDUNSPECIFIED
O’Shea, DUNSPECIFIEDUNSPECIFIED
Asberg, AUNSPECIFIEDUNSPECIFIED
Mueller, TUNSPECIFIEDUNSPECIFIED
Emery, VCUNSPECIFIEDUNSPECIFIED
Kumar, DUNSPECIFIEDUNSPECIFIED
Humar, HUNSPECIFIEDUNSPECIFIED
Date : 2015
Identification Number : 10.1111/ajt.13464
Copyright Disclaimer : This is the peer reviewed version of the following article: Egli, A., Lisboa, L. F., O'Shea, D., Asberg, A., Mueller, T., Emery, V., Kumar, D. and Humar, A. (2016), Complexity of Host Micro-RNA Response to Cytomegalovirus Reactivation After Organ Transplantation. American Journal of Transplantation, 16: 650–660. doi:10.1111/ajt.13464, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/ajt.13464/abstract.. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Depositing User : Symplectic Elements
Date Deposited : 21 Feb 2017 14:51
Last Modified : 31 Oct 2017 19:08
URI: http://epubs.surrey.ac.uk/id/eprint/813582

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