Cargando…

Upregulation of miRNA-4776 in Influenza Virus Infected Bronchial Epithelial Cells Is Associated with Downregulation of NFKBIB and Increased Viral Survival

Influenza A virus (IAV) infection remains a significant cause of morbidity and mortality worldwide. One key transcription factor that is activated upon IAV infection is nuclear factor Kappa B (NF-κB). NF-κB regulation involves the inhibitor proteins NF-κB inhibitor beta (NFKBIB), (also known as IκB...

Descripción completa

Detalles Bibliográficos
Autores principales: Othumpangat, Sreekumar, Bryan, Nicole B., Beezhold, Donald H., Noti, John D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454407/
https://www.ncbi.nlm.nih.gov/pubmed/28448456
http://dx.doi.org/10.3390/v9050094
_version_ 1783240827486601216
author Othumpangat, Sreekumar
Bryan, Nicole B.
Beezhold, Donald H.
Noti, John D.
author_facet Othumpangat, Sreekumar
Bryan, Nicole B.
Beezhold, Donald H.
Noti, John D.
author_sort Othumpangat, Sreekumar
collection PubMed
description Influenza A virus (IAV) infection remains a significant cause of morbidity and mortality worldwide. One key transcription factor that is activated upon IAV infection is nuclear factor Kappa B (NF-κB). NF-κB regulation involves the inhibitor proteins NF-κB inhibitor beta (NFKBIB), (also known as IκB β), which form complexes with NF-κB to sequester it in the cytoplasm. In this study, microarray data showed differential expression of several microRNAs (miRNAs) on exposure to IAV. Target scan analysis revealed that miR-4776, miR-4514 and miR-4742 potentially target NFKBIB messenger RNA (mRNA). Time-course analysis of primary bronchial epithelial cells (HBEpCs) showed that miR-4776 expression is increased within 1 h of infection, followed by its downregulation 4 h post-exposure to IAV. NFKBIB upregulation of miR-4776 correlated with a decrease in NFKBIB expression within 1 h of infection and a subsequent increase in NFKBIB expression 4 h post-infection. In addition, miRNA ago-immunoprecipitation studies and the three prime untranslated region (3’ UTR) luciferase assay confirmed that miR-4776 targets NFKBIB mRNA. Furthermore, uninfected HBEpCs transfected with miR-4776 mimic showed decreased expression of NFKBIB mRNA. Overexpression of NFKBIB protein in IAV infected cells led to lower levels of IAV. Taken together, our data suggest that miRNA-4776 modulates IAV production in infected cells through NFKBIB expression, possibly through the modulation of NF-κB.
format Online
Article
Text
id pubmed-5454407
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-54544072017-06-08 Upregulation of miRNA-4776 in Influenza Virus Infected Bronchial Epithelial Cells Is Associated with Downregulation of NFKBIB and Increased Viral Survival Othumpangat, Sreekumar Bryan, Nicole B. Beezhold, Donald H. Noti, John D. Viruses Article Influenza A virus (IAV) infection remains a significant cause of morbidity and mortality worldwide. One key transcription factor that is activated upon IAV infection is nuclear factor Kappa B (NF-κB). NF-κB regulation involves the inhibitor proteins NF-κB inhibitor beta (NFKBIB), (also known as IκB β), which form complexes with NF-κB to sequester it in the cytoplasm. In this study, microarray data showed differential expression of several microRNAs (miRNAs) on exposure to IAV. Target scan analysis revealed that miR-4776, miR-4514 and miR-4742 potentially target NFKBIB messenger RNA (mRNA). Time-course analysis of primary bronchial epithelial cells (HBEpCs) showed that miR-4776 expression is increased within 1 h of infection, followed by its downregulation 4 h post-exposure to IAV. NFKBIB upregulation of miR-4776 correlated with a decrease in NFKBIB expression within 1 h of infection and a subsequent increase in NFKBIB expression 4 h post-infection. In addition, miRNA ago-immunoprecipitation studies and the three prime untranslated region (3’ UTR) luciferase assay confirmed that miR-4776 targets NFKBIB mRNA. Furthermore, uninfected HBEpCs transfected with miR-4776 mimic showed decreased expression of NFKBIB mRNA. Overexpression of NFKBIB protein in IAV infected cells led to lower levels of IAV. Taken together, our data suggest that miRNA-4776 modulates IAV production in infected cells through NFKBIB expression, possibly through the modulation of NF-κB. MDPI 2017-04-27 /pmc/articles/PMC5454407/ /pubmed/28448456 http://dx.doi.org/10.3390/v9050094 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
Othumpangat, Sreekumar
Bryan, Nicole B.
Beezhold, Donald H.
Noti, John D.
Upregulation of miRNA-4776 in Influenza Virus Infected Bronchial Epithelial Cells Is Associated with Downregulation of NFKBIB and Increased Viral Survival
title Upregulation of miRNA-4776 in Influenza Virus Infected Bronchial Epithelial Cells Is Associated with Downregulation of NFKBIB and Increased Viral Survival
title_full Upregulation of miRNA-4776 in Influenza Virus Infected Bronchial Epithelial Cells Is Associated with Downregulation of NFKBIB and Increased Viral Survival
title_fullStr Upregulation of miRNA-4776 in Influenza Virus Infected Bronchial Epithelial Cells Is Associated with Downregulation of NFKBIB and Increased Viral Survival
title_full_unstemmed Upregulation of miRNA-4776 in Influenza Virus Infected Bronchial Epithelial Cells Is Associated with Downregulation of NFKBIB and Increased Viral Survival
title_short Upregulation of miRNA-4776 in Influenza Virus Infected Bronchial Epithelial Cells Is Associated with Downregulation of NFKBIB and Increased Viral Survival
title_sort upregulation of mirna-4776 in influenza virus infected bronchial epithelial cells is associated with downregulation of nfkbib and increased viral survival
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5454407/
https://www.ncbi.nlm.nih.gov/pubmed/28448456
http://dx.doi.org/10.3390/v9050094
work_keys_str_mv AT othumpangatsreekumar upregulationofmirna4776ininfluenzavirusinfectedbronchialepithelialcellsisassociatedwithdownregulationofnfkbibandincreasedviralsurvival
AT bryannicoleb upregulationofmirna4776ininfluenzavirusinfectedbronchialepithelialcellsisassociatedwithdownregulationofnfkbibandincreasedviralsurvival
AT beezholddonaldh upregulationofmirna4776ininfluenzavirusinfectedbronchialepithelialcellsisassociatedwithdownregulationofnfkbibandincreasedviralsurvival
AT notijohnd upregulationofmirna4776ininfluenzavirusinfectedbronchialepithelialcellsisassociatedwithdownregulationofnfkbibandincreasedviralsurvival