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Genetically determined resistance to infection by hepatotropic influenza A virus in mice: effect of immunosuppression
Abstract:
Mice carrying the gene Mx were resistant to the lethal action of a hepatotropic line of avian influenza A virus. In resistant animals, foci of liver necrosis were self-limiting, and maximal virus titers reached were much below those in susceptible animals. Resistance could not be abrogated by immunosuppressive treatment with cyclophosphamide, methotrexate, or procarbazine, although such treatment prevented cellular infiltration at sites of virus replication and appeared to delay virus clearance. Silica and thorium dioxide, thought to inhibit macrophage function, likewise failed to abolish resistance. Regenerating liver tissue did not support more extensive virus replication than did intact adult liver.
Insights
Mice with the Mx gene resist lethal avian influenza A virus. This resistance, observed in the liver, was not affected by immunosuppression or macrophage inhibition.
Area of Science:
- Virology
- Immunology
- Genetics
Background:
- Avian influenza A virus poses a significant threat to poultry and can cause severe disease in mammals.
- Understanding the genetic basis of resistance to influenza viruses is crucial for developing effective control strategies.
- The Mx gene has been implicated in innate antiviral responses, but its specific role in resistance to hepatotropic avian influenza A virus requires further investigation.
Purpose of the Study:
- To investigate the role of the Mx gene in conferring resistance to a hepatotropic avian influenza A virus in mice.
- To determine if immunosuppressive treatments or macrophage inhibition can overcome Mx-mediated resistance.
- To assess the impact of liver regeneration on viral replication in Mx-resistant mice.
Main Methods:
- Mice carrying the Mx gene were infected with a hepatotropic avian influenza A virus.
- Resistant and susceptible mice were monitored for survival, virus titers, and liver pathology.
- Immunosuppressive agents (cyclophosphamide, methotrexate, procarbazine) and macrophage inhibitors (silica, thorium dioxide) were administered to assess their effect on resistance.
- Viral replication was assessed in regenerating and intact adult liver tissues.
Main Results:
- Mice with the Mx gene exhibited resistance to the lethal effects of the avian influenza A virus.
- In resistant mice, liver necrosis foci were self-limiting, and peak virus titers were significantly lower compared to susceptible mice.
- Immunosuppressive treatments did not abolish Mx-mediated resistance but did inhibit cellular infiltration and delay virus clearance.
- Macrophage inhibition also failed to abrogate resistance.
- Regenerating liver tissue did not support enhanced viral replication compared to intact adult liver.
Conclusions:
- The Mx gene confers significant resistance to lethal hepatotropic avian influenza A virus infection in mice.
- Mx-mediated resistance is independent of the adaptive immune system and macrophage function.
- The liver's intrinsic defense mechanisms, potentially involving the Mx gene, play a critical role in controlling influenza A virus infection.