PDF(Pubmed)
Abstract：
Host factors play important roles in influenza A virus (IAV) replication. In order to identify novel host factors involved in IAV replication, we compared the differentially expressed genes in A549 cells after IAV infection. We found that lncRNA lnc-RPS6P3 was up-regulated upon viral infection and poly(I:C) and IFN-β treatment, indicating it was an interferon-stimulated gene. Functional analysis demonstrated that overexpression of lnc-RPS6P3 inhibited IAV replication while knockdown of lnc-RPS6P3 promoted viral infection in A549 cells. Lnc-RPS6P3 inhibited both transcription and replication of IAV. Further study showed that lnc-RPS6P3 interacted with viral NP and interfered with NP self-oligomerization and, consequently, inhibited vRNP activity. In addition, lnc-RPS6P3 interacted with viral NS1 and reduced the interaction of NS1 and RIG-I; it also attenuated the inhibitory effect of NS1 on IFN-β stimulation. In conclusion, we revealed that lnc-RPS6P3 is an interferon-stimulated gene that inhibits IAV replication and attenuates the inhibitory effect of NS1 on innate immune response.
摘要：
宿主因子在甲型流感病毒（IAV）复制中起重要作用。为了鉴定参与IAV复制的新宿主因子，我们比较了IAV感染后A549细胞中差异表达的基因。我们发现lncRNAlnc-RPS6P3在病毒感染和poly（I：C）和IFN-β处理后上调，表明是干扰素刺激的基因.功能分析显示,lnc-RPS6P3的过表达抑制IAV复制,而lnc-RPS6P3的敲低促进A549细胞中的病毒感染。Lnc-RPS6P3抑制IAV的转录和复制。进一步的研究表明，lnc-RPS6P3与病毒NP相互作用，干扰NP自身寡聚化，因此,抑制vRNP活性。此外,lnc-RPS6P3与病毒NS1相互作用并减少NS1和RIG-I的相互作用;它还减弱了NS1对IFN-β刺激的抑制作用。总之,我们发现lnc-RPS6P3是一种干扰素刺激的基因,能抑制IAV复制并减弱NS1对先天免疫应答的抑制作用.
