Small RNA Profiling of Influenza A Virus-Infected Cells Identifies miR-449b as a Regulator of Histone Deacetylase 1 and Interferon Beta

被引:34
作者
Buggele, William A. [1 ]
Krause, Katherine E. [1 ]
Horvath, Curt M. [1 ]
机构
[1] Northwestern Univ, Dept Mol Biosci, Evanston, IL 60208 USA
来源
PLOS ONE | 2013年 / 8卷 / 09期
关键词
MICRORNA EXPRESSION; CELLULAR MICRORNAS; GENE-EXPRESSION; INNATE IMMUNITY; RIG-I; PROTEIN; TRANSCRIPTION; OLIGONUCLEOTIDE; DEADENYLATION; REQUIREMENT;
D O I
10.1371/journal.pone.0076560
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mammalian antiviral response relies on the alteration of cellular gene expression, to induce the production of antiviral effectors and regulate their activities. Recent research has indicated that virus infections can induce the accumulation of cellular microRNA (miRNA) species that influence the stability of host mRNAs and their protein products. To determine the potential for miRNA regulation of cellular responses to influenza A virus infection, small RNA profiling was carried out using next generation sequencing. Comparison of miRNA expression profiles in uninfected human A549 cells to cells infected with influenza A virus strains A/Udorn/72 and A/WSN/33, revealed virus-induced changes in miRNA abundance. Gene expression analysis identified mRNA targets for a cohort of highly inducible miRNAs linked to diverse cellular functions. Experiments demonstrate that the histone deacetylase, HDAC1, can be regulated by influenza-inducible miR-449b, resulting in altered mRNA and protein levels. Expression of miR-449b enhances virus and poly(I: C) activation of the IFN beta promoter, a process known to be negatively regulated by HDAC1. These findings demonstrate miRNA induction by influenza A virus infection and elucidate an example of miRNA control of antiviral gene expression in human cells, defining a role for miR-449b in regulation of HDAC1 and antiviral cytokine signaling.
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页数:12
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