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

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 microRN...

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Autores principales: Deng, Jiang, Xiao, Jun, Ma, Ping, Gao, Bo, Gong, Feng, Lv, Liping, Zhang, Yanyu, Xu, Jinbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454430/
https://www.ncbi.nlm.nih.gov/pubmed/28534856
http://dx.doi.org/10.3390/v9050118
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author Deng, Jiang
Xiao, Jun
Ma, Ping
Gao, Bo
Gong, Feng
Lv, Liping
Zhang, Yanyu
Xu, Jinbo
author_facet Deng, Jiang
Xiao, Jun
Ma, Ping
Gao, Bo
Gong, Feng
Lv, Liping
Zhang, Yanyu
Xu, Jinbo
author_sort Deng, Jiang
collection PubMed
description 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.
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spelling pubmed-54544302017-06-08 Manipulation of Viral MicroRNAs as a Potential Antiviral Strategy for the Treatment of Cytomegalovirus Infection Deng, Jiang Xiao, Jun Ma, Ping Gao, Bo Gong, Feng Lv, Liping Zhang, Yanyu Xu, Jinbo Viruses Article 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. MDPI 2017-05-19 /pmc/articles/PMC5454430/ /pubmed/28534856 http://dx.doi.org/10.3390/v9050118 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Deng, Jiang
Xiao, Jun
Ma, Ping
Gao, Bo
Gong, Feng
Lv, Liping
Zhang, Yanyu
Xu, Jinbo
Manipulation of Viral MicroRNAs as a Potential Antiviral Strategy for the Treatment of Cytomegalovirus Infection
title Manipulation of Viral MicroRNAs as a Potential Antiviral Strategy for the Treatment of Cytomegalovirus Infection
title_full Manipulation of Viral MicroRNAs as a Potential Antiviral Strategy for the Treatment of Cytomegalovirus Infection
title_fullStr Manipulation of Viral MicroRNAs as a Potential Antiviral Strategy for the Treatment of Cytomegalovirus Infection
title_full_unstemmed Manipulation of Viral MicroRNAs as a Potential Antiviral Strategy for the Treatment of Cytomegalovirus Infection
title_short Manipulation of Viral MicroRNAs as a Potential Antiviral Strategy for the Treatment of Cytomegalovirus Infection
title_sort manipulation of viral micrornas as a potential antiviral strategy for the treatment of cytomegalovirus infection
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454430/
https://www.ncbi.nlm.nih.gov/pubmed/28534856
http://dx.doi.org/10.3390/v9050118
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