Studies on Heterotypic Interference between Influenza A and B Viruses: A Differential Inhibition of the Synthesis of Viral Proteins and RNAs

Abstract

Mixed infection of MDCK [Madin-Darby canine kidney] cells with influenza A and influenza B viruses leads to a reduction in the rate of synthesis of hemagglutinin (HA) and nucleoprotein (NP) as compared to their rate of synthesis in cells separately infected with these viruses. The reduction is much stronger for influenza A virus proteins. The synthesis of the nonstructural NS1 protein of both viruses is relatively resistant to the heterotypic interference. The synthesis of virus-specific mRNA exhibits the same pattern: the formation of the transcripts of HA and NP genes is much more drastically reduced than the synthesis of NS gene transcripts. The effect is strongly dependent on the multiplicity of infection and on the ratio of influenza A and B viruses in the inoculum. Primary transcription in the presence of cycloheximide is almost unchanged in doubly infected cells as compared to single infection, and no indication of differential inhibition has been observed. The results are discussed in connection with the mechanism of heterotypic interference and the regulation of influenza virus protein synthesis.