MicroRNA Regulation of Human Protease Genes Essential for Influenza Virus Replication

Influenza A virus causes seasonal epidemics and periodic pandemics threatening the health of millions of people each year. Vaccination is an effective strategy for reducing morbidity and mortality, and in the absence of drug resistance, the efficacy of chemoprophylaxis is comparable to that of vacci...

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Main Authors: Meliopoulos, Victoria A., Andersen, Lauren E., Brooks, Paula, Yan, Xiuzhen, Bakre, Abhijeet, Coleman, J. Keegan, Tompkins, S. Mark, Tripp, Ralph A.
Format: Online
Language:English
Published: Public Library of Science 2012
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351457/
id pubmed-3351457
recordtype oai_dc
spelling pubmed-33514572012-05-17 MicroRNA Regulation of Human Protease Genes Essential for Influenza Virus Replication Meliopoulos, Victoria A. Andersen, Lauren E. Brooks, Paula Yan, Xiuzhen Bakre, Abhijeet Coleman, J. Keegan Tompkins, S. Mark Tripp, Ralph A. Research Article Influenza A virus causes seasonal epidemics and periodic pandemics threatening the health of millions of people each year. Vaccination is an effective strategy for reducing morbidity and mortality, and in the absence of drug resistance, the efficacy of chemoprophylaxis is comparable to that of vaccines. However, the rapid emergence of drug resistance has emphasized the need for new drug targets. Knowledge of the host cell components required for influenza replication has been an area targeted for disease intervention. In this study, the human protease genes required for influenza virus replication were determined and validated using RNA interference approaches. The genes validated as critical for influenza virus replication were ADAMTS7, CPE, DPP3, MST1, and PRSS12, and pathway analysis showed these genes were in global host cell pathways governing inflammation (NF-κB), cAMP/calcium signaling (CRE/CREB), and apoptosis. Analyses of host microRNAs predicted to govern expression of these genes showed that eight miRNAs regulated gene expression during virus replication. These findings identify unique host genes and microRNAs important for influenza replication providing potential new targets for disease intervention strategies. Public Library of Science 2012-05-14 /pmc/articles/PMC3351457/ /pubmed/22606348 http://dx.doi.org/10.1371/journal.pone.0037169 Text en Meliopoulos et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Meliopoulos, Victoria A.
Andersen, Lauren E.
Brooks, Paula
Yan, Xiuzhen
Bakre, Abhijeet
Coleman, J. Keegan
Tompkins, S. Mark
Tripp, Ralph A.
spellingShingle Meliopoulos, Victoria A.
Andersen, Lauren E.
Brooks, Paula
Yan, Xiuzhen
Bakre, Abhijeet
Coleman, J. Keegan
Tompkins, S. Mark
Tripp, Ralph A.
MicroRNA Regulation of Human Protease Genes Essential for Influenza Virus Replication
author_facet Meliopoulos, Victoria A.
Andersen, Lauren E.
Brooks, Paula
Yan, Xiuzhen
Bakre, Abhijeet
Coleman, J. Keegan
Tompkins, S. Mark
Tripp, Ralph A.
author_sort Meliopoulos, Victoria A.
title MicroRNA Regulation of Human Protease Genes Essential for Influenza Virus Replication
title_short MicroRNA Regulation of Human Protease Genes Essential for Influenza Virus Replication
title_full MicroRNA Regulation of Human Protease Genes Essential for Influenza Virus Replication
title_fullStr MicroRNA Regulation of Human Protease Genes Essential for Influenza Virus Replication
title_full_unstemmed MicroRNA Regulation of Human Protease Genes Essential for Influenza Virus Replication
title_sort microrna regulation of human protease genes essential for influenza virus replication
description Influenza A virus causes seasonal epidemics and periodic pandemics threatening the health of millions of people each year. Vaccination is an effective strategy for reducing morbidity and mortality, and in the absence of drug resistance, the efficacy of chemoprophylaxis is comparable to that of vaccines. However, the rapid emergence of drug resistance has emphasized the need for new drug targets. Knowledge of the host cell components required for influenza replication has been an area targeted for disease intervention. In this study, the human protease genes required for influenza virus replication were determined and validated using RNA interference approaches. The genes validated as critical for influenza virus replication were ADAMTS7, CPE, DPP3, MST1, and PRSS12, and pathway analysis showed these genes were in global host cell pathways governing inflammation (NF-κB), cAMP/calcium signaling (CRE/CREB), and apoptosis. Analyses of host microRNAs predicted to govern expression of these genes showed that eight miRNAs regulated gene expression during virus replication. These findings identify unique host genes and microRNAs important for influenza replication providing potential new targets for disease intervention strategies.
publisher Public Library of Science
publishDate 2012
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351457/
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