Differential microRNA expression following infection with a mouse-adapted, highly virulent avian H5N2 virus

BMC Microbiology

Young-Ki Choi¹  Young-Il Kim¹  Semi Kim¹  Gyo-Jin Lim¹  Hyeok-il Kwon¹  Su-Jin Park¹  Philippe Noriel Q Pascua¹  Eun-Ha Kim¹  Yun Hee Baek¹  Hyeun Bum Kim²  Eun-Ji Choi¹ 

[1]College of Medicine and Medical Research Institute, Chungbuk National University, 12 Gaeshin-Dong Heungduk-Ku, Cheongju 361-763, Republic of Korea

[2]Department of Animal Resources Science, Dankook University, Dandae-ro 119, Cheonan 330-714, Republic of Korea

关键词: Replication;    Virulence;    Inhibitor;    MicroRNA;    Influenza A virus;   

Others  :  1170523
DOI  :  10.1186/s12866-014-0252-0

 received in 2014-07-05, accepted in 2014-09-23,  发布年份 2014

【 摘 要 】

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% (MLD₅₀) 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.

【 授权许可】

   
2014 Choi et al.; licensee BioMed Central Ltd.

【 图 表 】

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