Crucial role of PA in virus life cycle and host adaptation of influenza A virus.

The PA protein is the third subunit of the polymerase complex of influenza A virus. Compared with the other two polymerase subunits (PB2 and PB1), its precise functions are less defined. However, in recent years, advances in protein expression and crystallization technologies and also the reverse genetics, greatly accelerate our understanding of the essential role of PA in virus infection. Here, we first review the current literature on this remarkably multifunctional viral protein regarding virus life cycle, including viral RNA transcription and replication, viral genome packaging and assembly. We then discuss the various roles of PA in host adaption in avian species and mammals, general virus-host interaction, and host protein synthesis shutoff. We also review the recent findings about the novel proteins derived from PA. Finally, we discuss the prospects of PA as a target for the development of new antiviral approaches and drugs.