Abstract
Influenza A virus (IAV) is an obligatory intracellular microbial pathogen. It causes seasonal epidemics, occasional pandemics, and zoonotic outbreaks of an acute febrile respiratory disease called influenza, commonly known as flu, in humans. IAV is an enveloped virus and possesses a single-stranded, negative-sense RNA genome which has a linear but segmented configuration and is composed of eight gene segments. The non-structural 1 (NS1) protein is encoded by the eighth gene segment and, as the name suggests, is not packaged into IAV particles but found only in infected cells. NS1 is an IAV virulence factor, and the IAV mutants lacking NS1 exhibit attenuated phenotype. NS1 is composed of two major domains—the N-terminal RNA-binding domain and the C-terminal effector domain, which are joined by a small linker region, and the effector domain is flanked by a C-terminal tail. NS1 is truly a multi-functional protein and exploits or subverts multiple host pathways, e.g., mRNA splicing, nuclear export and translation, innate antiviral response, phosphatidylinositol-3-kinase signaling, to facilitate IAV multiplication and pathogenesis. This review summarizes the targeting of those host pathways and their components by NS1 and highlights the potential of NS1 as an antiviral drug target and the development of IAV NS1 mutants as a flu vaccine.