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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
Published on: March 2, 2014
Resistance to influenza virus and vesicular stomatitis virus conferred by expression of human MxA protein
J Pavlovic1, T Zürcher, O Haller
1Institut für Immunologie und Virologie, Universität Zürich, Switzerland.
Abstract:
MxA and MxB are interferon-induced proteins of human cells and are related to the murine protein Mx1, which confers selective resistance to influenza virus. In contrast to the nuclear murine protein Mx1, MxA and MxB are located in the cytoplasm, and their role in the interferon-induced antiviral state was unknown. In this report we show that transfected cell lines expressing MxA acquired a high degree of resistance to influenza A virus. Surprisingly, MxA also conferred resistance to vesicular stomatitis virus. Expression of MxA in transfected 3T3 cells had no effect on the multiplication of two picornaviruses, a togavirus, or herpes simplex virus type 1. Treatment of MxA-expressing cells with antibodies to mouse alpha-beta interferon did not abolish the resistance phenotype. The conclusion that resistance to influenza virus and vesicular stomatitis virus was due to the specific action of MxA is further supported by the observation that transfected 3T3 cell lines expressing the related MxB failed to acquire virus resistance.
Insights
Human MxA protein confers resistance to influenza A and vesicular stomatitis viruses. This interferon-induced protein, MxA, located in the cytoplasm, plays a key role in antiviral defense.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- MxA and MxB are interferon-induced human proteins.
- They are related to murine Mx1 protein, known for influenza resistance.
- Cytoplasmic localization of MxA/MxB contrasted with nuclear Mx1, leaving their antiviral role unknown.
Purpose of the Study:
- To investigate the role of MxA and MxB in the interferon-induced antiviral state.
- To determine if MxA confers resistance to specific viruses.
Main Methods:
- Transfected cell lines expressing MxA and MxB were created.
- Virus resistance assays were performed using influenza A, vesicular stomatitis virus, picornaviruses, togavirus, and herpes simplex virus type 1.
- Effect of anti-interferon antibodies on MxA-expressing cells was assessed.
Main Results:
- MxA expression in transfected cells conferred significant resistance to influenza A virus.
- MxA also unexpectedly conferred resistance to vesicular stomatitis virus.
- MxA did not affect the multiplication of picornaviruses, togavirus, or herpes simplex virus type 1.
- MxB expression did not confer virus resistance.
- Resistance phenotype in MxA-expressing cells was not abolished by anti-interferon antibodies.
Conclusions:
- MxA is a key mediator of resistance against influenza A and vesicular stomatitis viruses.
- The antiviral activity of MxA is specific and not dependent on alpha-beta interferon signaling.
- MxB does not appear to play a similar antiviral role.
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