Induction of MxA gene expression by influenza A virus requires type I or type III interferon signaling

Dirk Holzinger1, Carl Jorns, Silke Stertz

  • 1Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Hermann-Herder-Strasse 11, D-79104 Freiburg, Germany.

Journal of Virology
|May 12, 2007
PubMed

Insights

The MxA gene, crucial for antiviral defense, requires STAT1 signaling for induction by influenza viruses and interferons (IFNs). MxA expression is not directly triggered by viral infection, unlike ISG56.

Area of Science:

  • Virology
  • Immunology
  • Molecular Biology

Background:

  • The human MxA gene is an interferon-stimulated gene (ISG) vital for antiviral resistance against influenza viruses.
  • MxA is a well-established marker for interferon (IFN) bioactivity due to its transcriptional upregulation by type I and type III IFNs.

Purpose of the Study:

  • To investigate the specific requirements for MxA gene induction during influenza A virus infection.
  • To determine if viruses can directly activate MxA expression independently of secreted IFNs.

Main Methods:

  • Utilized an NS1-deficient influenza A virus and human cells with defects in IFN production or STAT1 signaling.
  • Employed real-time reverse transcriptase PCR to analyze MxA gene expression profiles.
  • Compared MxA induction with that of another IFN-stimulated gene, ISG56.

Main Results:

  • MxA gene expression was not induced by the NS1-deficient virus in IFN nonproducer cells or STAT1-null cells.
  • IFN-alpha and IFN-lambda did not significantly affect MxA expression in STAT1-null cells, confirming the necessity of STAT1 signaling.
  • The IFN-stimulated gene ISG56, however, was induced by the virus in these cells, indicating an IFN-independent induction pathway.

Conclusions:

  • MxA induction by influenza virus infection necessitates STAT1 signaling and is not directly triggered by the virus.
  • MxA serves as a specific and reliable marker for detecting type I and type III IFN activity in the context of viral infections and IFN-based therapies.

Related Concept Videos

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...
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...
Inhibitors Of Virion Release01:25

Inhibitors Of Virion Release

Viral replication and dissemination rely on efficient mechanisms for host cell entry, genome replication, assembly, and release. Influenza viruses, such as types A and B, are negative-sense single-stranded RNA viruses with a segmented genome, that depend on two critical surface glycoproteins to carry out these processes: hemagglutinin (HA) and neuraminidase (NA). HA initiates infection by binding to sialic acid residues on the surface of host epithelial cells, facilitating receptor-mediated...
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...
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...