1231. NF-ęB Activation is Modulated via Induction of MicroRNA 4776 Acting on NFęBIB Following Infection with Influenza H1N1 in Bronchial Epithelial Cells
Session: Poster Abstract Session: Viral Infections: Pathogenesis and Immunity
Friday, October 9, 2015
Room: Poster Hall
Background:

Influenza infection remains a significant source of morbidity and mortality worldwide. Recent studies have demonstrated that multiple changes in the miRNA profile can be detected in human serum in the presence of influenza infection. MiRNAs are small regulatory molecules, which influence protein expression through mediation of post-transcriptional silencing of target genes. These molecules have been shown to play a key role in the regulation of a diverse array of cellular responses including inflammation. One key transcription factor that is activated upon influenza infection is NF-κB. Regulation of NF-κB is a complex process involving both internal and external cellular stimuli. One mechanism of regulation involves a family of inhibitor proteins (IκB), which form complexes with NF-κB, and thereby sequester it into the cytoplasm. This effectively prevents nuclear translocation of NF-κB and therefore transcription of its target genes. Here, we identify a novel miRNA molecule, miR-4776, which is upregulated in response to influenza infection, and targets NFκBIB, thereby modulating NF-κB activity.

Methods:

Using Microarray analysis, we found that miR-4776 is upregulated in A549 cells following exposure to influenza virus, compared to uninfected control cells. Target scan analysis revealed NFκBIB as one target of this miRNA. Time-course analysis of both A549 cells as well as primary bronchial epithelial cells revealed that miR-4776 expression is increased within 1 hour of infection by quantitative PCR analysis, followed by a down-regulation by 4 hours of infection. Quantitative PCR also revealed that the initial increase in miR-4776 correlated with subsequent decrease in NFκBIB mRNA, and increase in NF-κB mRNA.

Results:

miR-4776 is upregulated in A549 cells following exposure to influenza virus, and NFkBIB is one target of this novel miRNA. miR-4776 expression is increased within one hour of infection, followed by a subsequent down-regulation. The initial increase in miR-4776 correlates with subsequent decrease in NFkBIB mRNA as well as an increase in NF-kB mRNA.

Conclusion:

Here, we identify a novel miRNA molecule involved in the regulation of the NF-κB pathway through targeting of the NFκBIB in response in influenza virus infection.

Nicole Bryan, MD/PhD1, Rashida Khakoo, MD, MACP, FIDSA, FSHEA2, John Noti, PhD3 and Sreekumar Othumpangat, PhD3, (1)Medicine, West Virginia University Section of Infectious Disease, Morgantown, WV, (2)Medicine, West Virginia University Section of Infectious Diseases, Morgantown, WV, (3)2. Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV

Disclosures:

N. Bryan, None

R. Khakoo, None

J. Noti, None

S. Othumpangat, None

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