Combined action of mouse alpha and beta interferons in influenza virus-infected macrophages carrying the resistance gene Mx.

In mice, the combined action of alpha and beta interferons (IFNs) against influenza viruses is modulated by the host gene Mx. High concentrations of IFN fail to prevent efficiently the replication of influenza A virus in cultured macrophages lacking the gene Mx, whereas cultured macrophages carrying Mx develop strong antiviral activity even at low concentrations of IFN. Several steps in the replication cycle of influenza virus were compared in Mx/Mx and +/+ mouse macrophages treated with IFN-alpha + beta. Uncoating was not affected. A twofold reduction in the accumulation of primary transcripts was observed in IFN-treated macrophages at the highest concentration of IFN regardless of the genetic constitution of the host cell. No evidence was obtained for inhibition of influenza virus translation in macrophages which lacked Mx when treated with IFN-alpha + beta. In contrast, a marked shut-off of influenza virus polypeptide synthesis occurred in Mx-bearing macrophages treated with these IFNs, although the primary transcripts were active in directing the synthesis of viral polypeptides in a cell-free system. We concluded that a specific inhibitory mechanism for influenza virus translation was induced by IFN-alpha + beta in macrophages bearing the resistance gene Mx.