Interferon-dependent Genetic Resistance to Influenza Virus in Mice: Virus Replication in Macrophages is Inhibited at an Early Step

Abstract

Inborn resistance to orthomyxoviruses due to the allele Mx was investigated at the molecular level in macrophages from A2G mice. In the absence of interferon, Mx-bearing and control cells were equally permissive for M-TUR, a macrophage-adapted strain of influenza A virus. After treatment with various doses of mouse interferon type I, Mx-bearing cells were fully resistant to this virus whereas cells lacking Mx were only marginally protected. Virus attachment and penetration were equally efficient in Mx-carrying and control cells and were not influenced by interferon. However, virus protein synthesis was blocked in Mx-bearing macrophages expressing resistance. These findings indicate that the resistance mechanism specific for influenza viruses realized by Mx in cooperation with interferon inhibits influenza virus replication in macrophages at an early stage following attachment and penetration of the virus.