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Differential microRNA expression following infection with a mouse-adapted, highly virulent avian H5N2 virus
BACKGROUND: MicroRNAs (miRNAs) are known to regulate various biological processes, including expression of cellular gene and virus-induced inflammation. Recently, studies have indicated that some miRNAs could regulate influenza virus replication. Due to differential sensitivities of influenza A viru...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189662/ https://www.ncbi.nlm.nih.gov/pubmed/25266911 http://dx.doi.org/10.1186/s12866-014-0252-0 |
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author | Choi, Eun-Ji Kim, Hyeun Bum Baek, Yun Hee Kim, Eun-Ha Pascua, Philippe Noriel Q Park, Su-Jin Kwon, Hyeok-il Lim, Gyo-Jin Kim, Semi Kim, Young-Il Choi, Young-Ki |
author_facet | Choi, Eun-Ji Kim, Hyeun Bum Baek, Yun Hee Kim, Eun-Ha Pascua, Philippe Noriel Q Park, Su-Jin Kwon, Hyeok-il Lim, Gyo-Jin Kim, Semi Kim, Young-Il Choi, Young-Ki |
author_sort | Choi, Eun-Ji |
collection | PubMed |
description | BACKGROUND: MicroRNAs (miRNAs) are known to regulate various biological processes, including expression of cellular gene and virus-induced inflammation. Recently, studies have indicated that some miRNAs could regulate influenza virus replication. Due to differential sensitivities of influenza A virus strains to different species (avian and mammalian), variations in host responses may be observed. Therefore, we investigated and compared the differences in global host miRNA expression in mouse lungs infected with wild type low pathogenicity A/Aquatic bird/Korea/w81/2005 (H5N2) (w81) or mouse-adapted virulent A/Aquatic bird /Korea/ma81/2007 (H5N2) (ma81) virus. RESULTS: Although the mice infected with ma81 exhibited much greater mortality than w81-infected mice, the parental w81 virus induced a higher number of differentially expressed miRNAs compared to the ma81 virus. Between these 2 viruses, a total of 27 and 20 miRNAs were commonly expressed at 1 dpi and 3 dpi, respectively. It is noteworthy that only 9 miRNAs (miR-100-5p, miR-130a-5p, miR-146b-3p, miR-147-3p, miR-151-5p, miR-155-3p, miR-223-3p, miR-301a-3p, and miR-495-3p) were significantly upregulated in both lungs infected with either wild type w81 or the mouse-adapted ma81 strain at both time points. Notably, expression levels of miR-147-3p, miR-151-5p, miR-155-3p, and miR-223-3p were higher in the lungs of mice infected with the ma81 virus than those infected with the w81 virus. To identify potential roles of these miRNAs in regulating influenza virus replication, each group of mice was intranasally treated with each inhibitor of specifically targeting 4 miRNAs, and then challenged with 5 mouse lethal dose 50% (MLD(50)) of the virulent ma81 virus on the following day. Although the specific miRNA inhibitors could not completely attenuate mortality or reduce viral replication, the miR-151-5p- and miR-223-3p-inhibitors reduced mortality of inoculated mice to 70% and substantially delayed death. CONCLUSIONS: Our results suggest that the mammalian adaptation of avian influenza A virus results in a different miRNA expression pattern in lungs of virus-infected mice compared with its parental strain, and use of specific miRNA inhibitors to target genes associated with the immune response or cell death may affect virulence and virus replication. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12866-014-0252-0) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4189662 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-41896622014-10-23 Differential microRNA expression following infection with a mouse-adapted, highly virulent avian H5N2 virus Choi, Eun-Ji Kim, Hyeun Bum Baek, Yun Hee Kim, Eun-Ha Pascua, Philippe Noriel Q Park, Su-Jin Kwon, Hyeok-il Lim, Gyo-Jin Kim, Semi Kim, Young-Il Choi, Young-Ki BMC Microbiol Research Article BACKGROUND: MicroRNAs (miRNAs) are known to regulate various biological processes, including expression of cellular gene and virus-induced inflammation. Recently, studies have indicated that some miRNAs could regulate influenza virus replication. Due to differential sensitivities of influenza A virus strains to different species (avian and mammalian), variations in host responses may be observed. Therefore, we investigated and compared the differences in global host miRNA expression in mouse lungs infected with wild type low pathogenicity A/Aquatic bird/Korea/w81/2005 (H5N2) (w81) or mouse-adapted virulent A/Aquatic bird /Korea/ma81/2007 (H5N2) (ma81) virus. RESULTS: Although the mice infected with ma81 exhibited much greater mortality than w81-infected mice, the parental w81 virus induced a higher number of differentially expressed miRNAs compared to the ma81 virus. Between these 2 viruses, a total of 27 and 20 miRNAs were commonly expressed at 1 dpi and 3 dpi, respectively. It is noteworthy that only 9 miRNAs (miR-100-5p, miR-130a-5p, miR-146b-3p, miR-147-3p, miR-151-5p, miR-155-3p, miR-223-3p, miR-301a-3p, and miR-495-3p) were significantly upregulated in both lungs infected with either wild type w81 or the mouse-adapted ma81 strain at both time points. Notably, expression levels of miR-147-3p, miR-151-5p, miR-155-3p, and miR-223-3p were higher in the lungs of mice infected with the ma81 virus than those infected with the w81 virus. To identify potential roles of these miRNAs in regulating influenza virus replication, each group of mice was intranasally treated with each inhibitor of specifically targeting 4 miRNAs, and then challenged with 5 mouse lethal dose 50% (MLD(50)) of the virulent ma81 virus on the following day. Although the specific miRNA inhibitors could not completely attenuate mortality or reduce viral replication, the miR-151-5p- and miR-223-3p-inhibitors reduced mortality of inoculated mice to 70% and substantially delayed death. CONCLUSIONS: Our results suggest that the mammalian adaptation of avian influenza A virus results in a different miRNA expression pattern in lungs of virus-infected mice compared with its parental strain, and use of specific miRNA inhibitors to target genes associated with the immune response or cell death may affect virulence and virus replication. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12866-014-0252-0) contains supplementary material, which is available to authorized users. BioMed Central 2014-09-30 /pmc/articles/PMC4189662/ /pubmed/25266911 http://dx.doi.org/10.1186/s12866-014-0252-0 Text en © Choi et al.; licensee BioMed Central Ltd. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Choi, Eun-Ji Kim, Hyeun Bum Baek, Yun Hee Kim, Eun-Ha Pascua, Philippe Noriel Q Park, Su-Jin Kwon, Hyeok-il Lim, Gyo-Jin Kim, Semi Kim, Young-Il Choi, Young-Ki Differential microRNA expression following infection with a mouse-adapted, highly virulent avian H5N2 virus |
title | Differential microRNA expression following infection with a mouse-adapted, highly virulent avian H5N2 virus |
title_full | Differential microRNA expression following infection with a mouse-adapted, highly virulent avian H5N2 virus |
title_fullStr | Differential microRNA expression following infection with a mouse-adapted, highly virulent avian H5N2 virus |
title_full_unstemmed | Differential microRNA expression following infection with a mouse-adapted, highly virulent avian H5N2 virus |
title_short | Differential microRNA expression following infection with a mouse-adapted, highly virulent avian H5N2 virus |
title_sort | differential microrna expression following infection with a mouse-adapted, highly virulent avian h5n2 virus |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189662/ https://www.ncbi.nlm.nih.gov/pubmed/25266911 http://dx.doi.org/10.1186/s12866-014-0252-0 |
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