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

Abstract

SUMMARYMixed infection of MDCK cells with influenza A and influenza B viruses leads to a reduction in the rate of synthesis of haemagglutinin (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 mRNAs 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.

Mechanism of Interference Between Influenza A/WSN and B/Kanagawa Viruses

“…Similar results were also described by Tobita & Ohori (1979), and preferential suppression of the expression of the HA and NP genes of influenza A virus has recently been reported by Kaverin et al (1983). We could not determine the inhibitory effect of B/Kanagawa on the synthesis of the A/WSN HA polypeptide, because of its poor incorporation of radioactive methionine.…”

“…In simultaneously co-infected cells, these polypeptides of both type A and type B viruses, except for NS of B/Kanagawa, were synthesized in reduced amounts (lane 2). A similar observation has been described by Kaverin et al (1983). When NP bands were cut from the gel and examined for their radioactivities, the results showed that the amounts of N P of A / W S N and B/Kanagawa in simultaneously co-infected cells were 27 ~ and 41 ~ respectively of those in singly infected cultures.…”

“…When virus replication in simultaneously coinfected cells was restricted to primary transcription by cycloheximide, the translation products of both virus types were clearly detected, suggesting that simultaneous co-infection induces primary transcription of both type A and type B virus genomes, although the possibility of mutual interference at the level of primary transcription remains to be tested. More recent evidence has been presented by Kaverin et al (1983), suggesting that intertypic interference occurs not at the level of primary transcription but at subsequent transcription. Taken together, the interference between influenza A and B viruses at the ievel of transcription may explain in part why there is no genetic interaction between influenza A and B type viruses (Sugiura, 1975).…”

“…In spite of many similarities in biological properties and structure between type A and type B viruses, intertypic recombination has not been demonstrated (Sugiura, 1975). However, simultaneous infection with A and B type viruses results in interference with the multiplication of one or both viruses, depending on the multiplicity of infection (Gotlieb & Hirst, 1954;Tobita & Ohori, 1979;Mikheeva & Ghendon, 1982;Kaverin et al, 1983).…”

“…Recent studies on the molecular basis of interference between influenza A and B viruses have suggested that it is exerted at the level of primary transcription (Mikheeva & Ghendon, 1982) or at later transcriptional events (Kaverin et al, 1983). Rottet al (1981) have demonstrated that even homotypic interactions between influenza A viruses differ in outcome, depending on the time of superinfection as well as the multiplicity of the inocula: simultaneous co-infection with swine virus and fowl plague virus (FPV) results in interference with swine virus only, while superinfection by FPV l h after swine virus infection leads to genetic interaction.…”