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Updated: Jul 15, 2026

Co-immunoprecipitation of the Mouse Mx1 Protein with the Influenza A Virus Nucleoprotein
Published on: April 21, 2015
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.
Abstract:
The human MxA gene belongs to the class of interferon (IFN)-stimulated genes (ISGs) involved in antiviral resistance against influenza viruses. Here, we studied the requirements for MxA induction by influenza A virus infection. MxA is transcriptionally upregulated by type I (alpha and beta) and type III (lambda) IFNs. Therefore, MxA is widely used in gene expression studies as a reliable marker for IFN bioactivity. It is not known, however, whether viruses can directly activate MxA expression in the absence of secreted IFN. By using an NS1-deficient influenza A virus and human cells with defects in IFN production or the STAT1 gene, we studied the induction profile of MxA by real-time reverse transcriptase PCR. The NS1-deficient virus is known to be a strong activator of the IFN system because NS1 acts as a viral IFN-antagonistic protein. Nevertheless, MxA gene expression was not inducible by this virus upon infection of IFN nonproducer cells and STAT1-null cells. Likewise, neither IFN-alpha nor IFN-lambda had a sizeable effect on the STAT1-null cells, indicating that MxA expression requires STAT1 signaling and cannot be triggered directly by virus infection. In contrast, the expression of the IFN-stimulated gene ISG56 was induced by influenza virus in these cells, confirming that ISG56 differs from MxA in being directly inducible by viral triggers in an IFN-independent way. In summary, our study reveals that MxA is a unique marker for the detection of type I and type III IFN activity during virus infections and IFN therapy.
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.
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