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Manipulation of Viral MicroRNAs as a Potential Antiviral Strategy for the Treatment of Cytomegalovirus Infection


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1

Beijing Key Laboratory of Blood Safety and Supply Technologies, Beijing 100850, China

2

Beijing Institute of Transfusion Medicine, 27 9 Taiping Road, Beijing 100850, China

3

Department of Blood Transfusion, Air Force General Hospital, Beijing 100142, China





*

Authors to whom correspondence should be addressed.



Academic Editor: Curt Hagedorn

Abstract Cytomegalovirus CMV infection leads to notable morbidity and mortality in immunosuppressed patients. Current antiviral drugs are effective but seriously limited in their long-term use due to their relatively high toxicity. In the present study, we characterized the expression of murine CMV microRNAs MCMV miRNAs both in vitro and in vivo. Although 29 miRNAs were detectable during in vitro infection, only 11 miRNAs classified as Group 1 were detectable during in vivo infection, and as many as 18 viral miRNAs classified as Group 2 were less detectable <50% of animals in both the liver and lungs. In addition, viral miRNA profiles in the blood revealed unstable and reduced expression. We next explored the in vitro effects of viral miRNAs on MCMV replication. The inhibition of Group 1 viral miRNAs had little effect on virus production, but transfected cells overexpressing miR-m01-3-5p, miR-M23-1-5p, miR-M55-1, and miR-m107-1-5p in Group 2 showed statistically lower viral loads than those transfected with control miRNA 29%, 29%, 39%, and 43%, respectively, versus control. Finally, we performed hydrodynamic injection of viral miRNA agomirs and observed lower levels of MCMV recurrence in the livers of animals overexpressing the miR-m01-3-5p or mcmv-miR-M23-1-5p agomirs compared with those of animals transfected with control agomir, confirming the antiviral effects of viral miRNA manipulation in vivo. Therefore, the manipulation of viral miRNA expression shows great therapeutic potential and represents a novel antiviral strategy for the miRNA-based treatment of cytomegalovirus infection. View Full-Text

Keywords: cytomegalovirus; viral miRNA; antiviral therapy; transfection cytomegalovirus; viral miRNA; antiviral therapy; transfection





Autor: Jiang Deng 1,2, Jun Xiao 3, Ping Ma 1,2, Bo Gao 1,2, Feng Gong 1,2, Liping Lv 1,2,* , Yanyu Zhang 1,2,* and Jinbo Xu 1,2,*

Fuente: http://mdpi.com/



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