Revisiting influenza A virus life cycle from a perspective of genome balance

Influenza A virus (IAV) genome comprises eight negative-sense RNA segments, of which the replication is well orchestrated and the delicate balance of multiple segments are dynamically regulated throughout IAV life cycle. However, previous studies seldom discuss these balances except for functional hemagglutinin-neuraminidase balance that is pivotal for both virus entry and release. Therefore, we attempt to revisit IAV life cycle by highlighting the critical role of “genome balance”. Moreover, we raise a “balance regression” model of IAV evolution that the virus evolves to rebalance its genome after reassortment or interspecies transmission, and direct a “balance compensation” strategy to rectify the “genome imbalance” as a result of artificial modifications during creation of recombinant IAVs. This review not only improves our understanding of IAV life cycle, but also facilitates both basic and applied research of IAV in future.