Abstract
The non-structural protein 1 (NS1) of influenza A viruses plays important roles in viral fitness and in the process of interspecies adaptation. It is one of the most polymorphic and mutation-tolerant proteins of the influenza A genome, but its evolutionary patterns in different host species and the selective pressures that underlie them are hard to define. In this review, we highlight some of the species-specific molecular signatures apparent in different NS1 proteins and discuss two functions of NS1 in the process of viral adaptation to new host species. First, we consider the ability of NS1 proteins to broadly suppress host protein expression through interaction with CPSF4. This NS1 function can be spontaneously lost and regained through mutation and must be balanced against the need for host co-factors to aid efficient viral replication. Evidence suggests that this function of NS1 may be selectively lost in the initial stages of viral adaptation to some new host species. Second, we explore the ability of NS1 proteins to inhibit antiviral interferon signaling, an essential function for viral replication without which the virus is severely attenuated in any host. Innate immune suppression by NS1 not only enables viral replication in tissues, but also dampens the adaptive immune response and immunological memory. NS1 proteins suppress interferon signaling and effector functions through a variety of protein-protein interactions that may differ from host to host but must achieve similar goals. The multifunctional influenza A virus NS1 protein is highly plastic, highly versatile, and demonstrates a diversity of context-dependent solutions to the problem of interspecies adaptation.
Highlights
The human-animal interface is impacted by ecological change and human encroachment, and zoonotic spillover continues to challenge human health and agriculture
A general summary of host-specific signatures in the non-structural protein 1 (NS1) protein is followed by a detailed discussion of two specific functions – the suppression of host protein synthesis and the inhibition of antiviral interferon signaling by the host retinoic acid-inducible gene I (RIG-I) pathway
Two regions in the nucleotide sequence of the NS genomic segment produce hairpins in their positivesense transcripts with species-specific structural differences, the significance of which is still unclear (Vasin et al, 2016). It is clear from deletion and mutation studies that a functional NS1 protein is absolutely essential for successful influenza A viruses (IAVs) replication in any host
Summary
The human-animal interface is impacted by ecological change and human encroachment, and zoonotic spillover continues to challenge human health and agriculture. The adaptation of viruses to new host species remains a relevant subject of investigation, and influenza A viruses (IAVs) offer many interesting examples. Recent strides have been made in understanding the evolutionary pressures that drive IAV host adaptation and the pathways to development of airborne transmission. IAV NS1 in Cross-Species Adaptation in new hosts. The evolution of the viral surface glycoproteins and their roles in cross-species transmission are well known and adaptation of the viral polymerase components to new cellular environments is necessary for efficient viral replication (Rogers and Paulson, 1983; De Graaf and Fouchier, 2014; Long et al, 2019). The selective pressures that drive evolution of the principle IAV immune antagonist, the non-structural protein 1 (NS1), have been more elusive. A general summary of host-specific signatures in the NS1 protein is followed by a detailed discussion of two specific functions – the suppression of host protein synthesis and the inhibition of antiviral interferon signaling by the host retinoic acid-inducible gene I (RIG-I) pathway
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