Abstract: A large number of recent researches show that the non-structural (A/NS1) protein of influenza A viruses is a non-essential virulence factor that has a multiple accessory functions during viral infection, which provide the important referece values for revealing the pathogenic mechanism of this zoonotic virus. Here, we review the current literature on this remarkably multifunctional viral protein, including its synthesis, structure, intracellular localization and roles in these processes such as viral replication, host innate and adaptive immune responses as well as cell signal transduction. This paper focus on the NS1-RNA and NS1-protein interactions that is fundamental to these processes. And highlight apparent strain-specific ways in which different NS1 proteins may act, in regards this, the contributions of certain NS1 functions to the pathogenicity of human and animal influenza A viruses are also discussed. Finally, we outline practical applications that future studies on NS1 may lead to, including the rational design and manufacture of influenza vaccines, the development of novel antiviral drugs, and the use of oncolytic influenza A viruses as potential anti-cancer agents. By the way, A/NS1 is compared with the NS1 of influenza B/C viruses.

Key words: influenza A viruses; non-structural protein 1; immune responses; cell signal pathway; virulence; pathogenicity