Development and applications of single-cycle infectious influenza A virus (sciIAV)

•Influenza A virus infections cause both seasonal epidemics and occasional pandemics.•SciIAVs are defective in viral replication or propagation.•Biocontained sciIAV can be used to study highly pathogenic influenza A viruses at BSL-2.•Expression of a reporter gene has allowed the use of sciIAVs in HTS settings.•SciIAVs have been used as potential safe vaccines or delivery vectors in mammals.

The diverse host range, high transmissibility, and rapid evolution of influenza A viruses justify the importance of containing pathogenic viruses studied in the laboratory. Other than physically or mechanically changing influenza A virus containment procedures, modifying the virus to only replicate for a single round of infection similarly ensures safety and consequently decreases the level of biosafety containment required to study highly pathogenic members in the virus family. This biological containment is more ideal because it is less apt to computer, machine, or human error. With many necessary proteins that can be deleted, generation of single-cycle infectious influenza A viruses (sciIAV) can be achieved using a variety of approaches. Here, we review the recent burst in sciIAV generation and summarize the applications and findings on this important human pathogen using biocontained viral mimics.