Mechanism of interference by defective-interfering particles of influenza virus: Differential reduction of intracellular synthesis of specific polymerase proteins

Defective-interfering (DI) influenza viruses interfere with the multiplication of standard influenza viruses in infected cells leading to a decreased amount of virus production. In this paper we show that the synthesis of one or more polymerase proteins relative to another is specifically decreased in cells coinfected with standard virus and DI virus preparations when compared to cells infected with standard virus alone. Furthermore, this decrease corresponds to the levels of specific polymerase mRNAs which in turn are proportional to the ratio of polymerase genes in the input DI virus. Decreased levels of specific polymerase transcripts and polymerase proteins are evident during both primary and secondary transcription. Although intracellular levels of different polymerase proteins may vary, they are present in approximately equimolar ratios in DI particles released from infected cells. Interference by influenza DI particles can be partially reversed by increasing the multiplicity of standard virus particles. Based on these observations a possible model for DI-mediated interference in influenza virus is discussed.