PDF(Pubmed)
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.
摘要：
甲型流感病毒的非结构蛋白1（NS1）在病毒适应性和种间适应过程中起着重要作用。它是甲型流感基因组中最具多态性和突变耐受性的蛋白质之一，但是它在不同宿主物种中的进化模式以及它们背后的选择压力很难定义。在这次审查中,我们强调了一些在不同NS1蛋白中明显的物种特异性分子特征,并讨论了NS1在病毒适应新宿主物种过程中的两种功能.首先,我们认为NS1蛋白通过与CPSF4相互作用广泛抑制宿主蛋白表达的能力。这种NS1功能可以自发地丧失并通过突变恢复,并且必须与宿主辅因子的需要相平衡以帮助有效的病毒复制。有证据表明，NS1的这种功能可能在病毒适应某些新宿主物种的初始阶段选择性丧失。第二,我们探索NS1蛋白抑制抗病毒干扰素信号的能力，病毒复制的基本功能，没有它，病毒在任何宿主中都会严重减毒。NS1的先天免疫抑制不仅使病毒在组织中复制，但也会抑制适应性免疫反应和免疫记忆。NS1蛋白通过各种蛋白质-蛋白质相互作用抑制干扰素信号传导和效应子功能，这些相互作用可能因宿主而异，但必须实现类似的目标。多功能甲型流感病毒NS1蛋白具有高度可塑性，高度多才多艺，并展示了物种间适应问题的多种上下文相关解决方案。
