Productive and non-productive phases during long-term persistence of influenza C virus

Persistent infection with a variant of influenza C/Ann Arbor/1/50 virus in MDCK cells has been previously reported. However, the precise molecular mechanism of persistence is still unknown. We show that the release of active progeny virus, as tested for by haemagglutination and acetylesterase profiles, does not take place in freshly seeded MDCK cells. Productive virus replication occurs simultaneously with massive production of structural proteins as shown by immunoprecipitation and immunofluorescence. PCR for the HEF structural protein-encoding segment 4 revealed that positive-sense RNA is present only during virus multiplication whereas negative-sense RNA appears to be constantly detectable. In this study we give initial evidence that influenza C virus can persist in the form of its genomic minus strand RNA, and plus strand transcription, protein synthesis and virus replication remain restricted to productive phases.