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Interferon-induced protein Mx accumulates in nuclei of mouse cells expressing resistance to influenza viruses
Abstract:
In mouse cells carrying the dominant influenza resistance allele Mx+ (but not in Mx- cells) interferon-alpha/beta (IFN) induces an efficient antiviral state against influenza viruses and, concomitantly, the synthesis of a 75,000-Da protein (protein Mx). Here, indirect immunofluorescence using monoclonal antibodies was used to demonstrate that protein Mx accumulates in the nucleus of IFN-treated Mx+ cells, suggesting a nuclear site of action. Protein Mx is present in the nucleus of untreated influenza virus-resistant macrophages freshly explanted from the peritoneal cavity of Mx+ mice but is lost with time in culture when peritoneal macrophages become permissive for influenza virus.
Insights
Interferon induces antiviral protein Mx in resistant mouse cells, which accumulates in the nucleus. This nuclear localization suggests protein Mx acts in the nucleus to confer influenza virus resistance.
Area of Science:
- Virology
- Immunology
- Cell Biology
Background:
- Interferon-alpha/beta (IFN) induces an antiviral state in mouse cells with the Mx+ allele.
- This antiviral state is accompanied by the synthesis of a 75,000-Da protein, termed protein Mx.
- Mx+ cells exhibit resistance to influenza viruses, while Mx- cells do not.
Purpose of the Study:
- To investigate the cellular localization of protein Mx in response to interferon treatment.
- To determine if the nuclear localization of protein Mx correlates with influenza virus resistance.
Main Methods:
- Indirect immunofluorescence using monoclonal antibodies was employed to detect protein Mx.
- Analysis was performed on interferon-treated Mx+ mouse cells and freshly explanted peritoneal macrophages from Mx+ mice.
Main Results:
- Protein Mx was observed to accumulate in the nucleus of interferon-treated Mx+ cells.
- Protein Mx was detected in the nucleus of untreated, influenza virus-resistant macrophages from Mx+ mice.
- The presence of protein Mx in the nucleus was diminished over time in cultured macrophages, coinciding with a loss of viral resistance.
Conclusions:
- Protein Mx accumulates in the nucleus of interferon-induced antiviral states in Mx+ cells.
- The nuclear localization of protein Mx suggests a nuclear site of action for conferring influenza virus resistance.
- Loss of nuclear protein Mx in cultured macrophages correlates with increased susceptibility to influenza virus infection.