In Transition: How Influenza Virus Switches from Transcription to Genome Replication

Influenza virus is a segmented, single-stranded, negative-sense RNA virus. Viral genome transcription (to make viral messenger RNA) and replication (to make more viral genome) of influenza virus are catalyzed by the influenza viral RNA-dependent RNA polymerase (FluPol) in the context of the viral ribonucleoprotein complexes in the nucleus of infected cells. The dynamics of the transcription and replication are tightly regulated throughout the viral life cycle, with a switch from transcription to replication in the later stages of infection being essential for efficient progeny virus production. The mechanism by which the virus achieves the switch has emerged recently through structural and functional studies. Here, we summarize the current hypotheses of the regulatory mechanisms governing the switch. Specifically, we highlight our recent findings showing that the late expression of the viral nonstructural protein NS2, which resulted from a suboptimal splicing site in the NS segment, functions as a molecular timer to mediate the transcription-to-replication switch.