title: MicroRNA regulation of human protease genes essential for influenza virus replication.
abstract: 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.
authors.affiliation: Department of Infectious Diseases, University of Georgia, Athens, Georgia, United States of America.
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Meliopoulos
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Andersen
authors.forename: Paula
authors.initials: P
authors.lastname: Brooks
authors.forename: Xiuzhen
authors.initials: X
authors.lastname: Yan
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Bakre
authors.forename: J Keegan
authors.initials: JK
authors.lastname: Coleman
authors.forename: S Mark
authors.initials: SM
authors.lastname: Tompkins
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Tripp
mesh_terms: D051722:ADAM Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D000071118:ADAMTS7 Protein; D001483:Base Sequence; D043423:Carboxypeptidase H / Q000037:antagonists & inhibitors / Q000235:genetics; D002460:Cell Line; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000037:antagonists & inhibitors / Q000235:genetics; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000502:physiology; D006801:Humans; D009980:Influenza A virus / Q000472:pathogenicity / Q000502:physiology*; D007251:Influenza, Human / Q000201:enzymology / Q000235:genetics / Q000821:virology; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs / Q000235:genetics*; D010447:Peptide Hydrolases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics; D014779:Virus Replication / Q000235:genetics*; D000099317:Hippo Kinases
chemical_list: D051722:ADAM Proteins; D000071118:ADAMTS7 Protein; D043423:Carboxypeptidase H; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D010447:Peptide Hydrolases; D017346:Protein Serine-Threonine Kinases; D034741:RNA, Small Interfering; D012697:Serine Endopeptidases; C095566:STK4 protein, human; D000099317:Hippo Kinases; C539603:DPP3 protein, human; C108493:neurotrypsin; C121534:ADAMTS7 protein, human