Identification of Host Kinase Genes Required for Influenza Virus Replication and the Regulatory Role of MicroRNAs

Abhijeet Bakre1, Lauren E Andersen, Victoria Meliopoulos

  • 1Department of Infectious Diseases, University of Georgia, Athens, Georgia, United States of America.

Plos One
|June 28, 2013
PubMed

Insights

This study identified essential human protein kinases (HPKs) crucial for influenza virus replication. MicroRNAs (miRNAs) were found to regulate these HPKs, offering new targets for antiviral strategies.

Area of Science:

  • Virology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Human protein kinases (HPKs) play critical roles in cellular processes.
  • Understanding host factors influencing influenza virus replication is vital for developing antiviral therapies.

Purpose of the Study:

  • To identify HPKs essential for influenza A virus replication.
  • To investigate the role of microRNAs (miRNAs) in regulating these HPKs during infection.

Main Methods:

  • A small interfering RNA (siRNA) screen of 720 HPKs was conducted.
  • Validation of identified HPKs for influenza virus replication.
  • Analysis of miRNA regulation on specific HPKs using agonists and antagonists.

Main Results:

  • 17 HPKs were essential for A/WSN/33 influenza virus replication.
  • 6 HPKs were vital for both A/WSN/33 and A/New Caledonia/20/99 influenza virus replication.
  • Specific miRNAs (miR-149*, miR-548d-3p, miR-1228, miR-138, miR-34c) were shown to regulate key HPKs (NEK8, MAPK1, CDK13, PLK4).
  • Upregulation of miR-34c enhanced viral replication by inducing PLK4 expression.

Conclusions:

  • This study identifies critical HPKs involved in influenza virus replication.
  • MiRNAs are key regulators of these HPKs, presenting potential therapeutic targets for influenza.
  • The findings provide insights into host-virus interactions and miRNA-mediated regulation of viral replication.

Related Concept Videos

Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R stands for...
Influenza01:27

Influenza

Influenza is an acute, highly communicable viral disease that affects the respiratory tract and is responsible for seasonal epidemics worldwide. Influenza A is the most prevalent type associated with widespread outbreaks and is subtyped based on two surface glycoproteins: hemagglutinin (H) and neuraminidase (N), as in H1N1. These glycoproteins are essential for viral infectivity, transmission, and immune recognition. Transmission occurs primarily through respiratory droplets and contaminated...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...
MicroRNAs01:22

MicroRNAs

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns—non-coding regions of a gene—or intergenic regions—stretches of DNA present between genes. Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA ends...