Abstract
Influenza A virus (IAV) is a segmented, negative single-stranded RNA virus that causes seasonal epidemics and has a potential for pandemics. Several viral proteins are not packed in the IAV viral particle and only expressed in the infected host cells. These proteins are named non-structural proteins (NSPs), including NS1, PB1-F2 and PA-X. They play a versatile role in the viral life cycle by modulating viral replication and transcription. More importantly, they also play a critical role in the evasion of the surveillance of host defense and viral pathogenicity by inducing apoptosis, perturbing innate immunity, and exacerbating inflammation. Here, we review the recent advances of these NSPs and how the new findings deepen our understanding of IAV–host interactions and viral pathogenesis.
Highlights
Influenza A virus (IAV) is a highly transmissible respiratory pathogen with the ability to cause seasonal epidemics and occasional pandemics, posing a considerable threat to global health [1,2,3,4].IAV belongs to the Orthomyxoviridae family, featuring a segmented genome [5]
NS2 has not yet been found to be associated with the endomembrane that is required for viral ribonucleoprotein complexes (vRNPs) trafficking, it was reported that NS2 interacts with the plasma membrane-associated F1Fo ATPase [91]
It will be interesting to know whether NS2 accompanies vRNP during trafficking to the cell membrane, or whether NS2 directs vRNP to the endomembrane system after nuclear export
Summary
Influenza A virus (IAV) is a highly transmissible respiratory pathogen with the ability to cause seasonal epidemics and occasional pandemics, posing a considerable threat to global health [1,2,3,4]. IAV has eight single-stranded, negative-sense viral RNA segments, which encode at least 10 proteins, including hemagglutinin (HA), neuraminidase (NA), matrix proteins 1 (M1) and 2 (M2), polymerase acidic (PA), polymerase basic 1 (PB1), polymerase basic 2 (PB2), nucleoprotein (NP), non-structural proteins 1. IAV infection starts with the binding of HA to the sialic acid of host cell membrane receptors. IAV expresses many non-structural proteins (NSPs), such as NS1, which are not packed in the IAV viral particle, but only expressed in the infected host cells. Most of them are generated from the splicing, frame shift and truncation of the coding region of structural proteins (Figure 1) They are not essential (except NS2), NSPs have emerged as having crucial roles in host defense suppression, virulence and pathogenicity (Figure 2). We discuss the role of NS1 in each aspect below in detail
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