MicroRNA regulation of human protease genes essential for influenza virus replication

PLoS One. 2012;7(5):e37169. doi: 10.1371/journal.pone.0037169. Epub 2012 May 14.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • ADAM Proteins / antagonists & inhibitors
  • ADAM Proteins / genetics
  • ADAMTS7 Protein
  • Base Sequence
  • Carboxypeptidase H / antagonists & inhibitors
  • Carboxypeptidase H / genetics
  • Cell Line
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / antagonists & inhibitors
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / genetics
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / physiology
  • Humans
  • Influenza A virus / pathogenicity
  • Influenza A virus / physiology*
  • Influenza, Human / enzymology
  • Influenza, Human / genetics
  • Influenza, Human / virology
  • MicroRNAs / genetics*
  • Peptide Hydrolases / genetics*
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / genetics
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Serine Endopeptidases / genetics
  • Virus Replication / genetics*

Substances

  • MicroRNAs
  • RNA, Small Interfering
  • STK4 protein, human
  • Protein-Serine-Threonine Kinases
  • Peptide Hydrolases
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • DPP3 protein, human
  • Carboxypeptidase H
  • Serine Endopeptidases
  • neurotrypsin
  • ADAM Proteins
  • ADAMTS7 Protein
  • ADAMTS7 protein, human