Biochemistry and Molecular Biophysics Graduate Group, University of Pennsylvania, Philadelphia, United States.
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, United States.
Elife. 2020 Dec 3;9:e55500. doi: 10.7554/eLife.55500.
Viral infection induces the expression of numerous host genes that impact the outcome of infection. Here, we show that infection of human lung epithelial cells with influenza A virus (IAV) also induces a broad program of alternative splicing of host genes. Although these splicing-regulated genes are not enriched for canonical regulators of viral infection, we find that many of these genes do impact replication of IAV. Moreover, in several cases, specific inhibition of the IAV-induced splicing pattern also attenuates viral infection. We further show that approximately a quarter of the IAV-induced splicing events are regulated by hnRNP K, a host protein required for efficient splicing of the IAV M transcript in nuclear speckles. Finally, we find an increase in hnRNP K in nuclear speckles upon IAV infection, which may alter accessibility of hnRNP K for host transcripts thereby leading to a program of host splicing changes that promote IAV replication.
病毒感染会诱导大量宿主基因的表达，从而影响感染的结果。在这里，我们表明，甲型流感病毒（IAV）感染人肺上皮细胞也会诱导宿主基因的广泛选择性剪接程序。尽管这些剪接调控基因没有富集到经典的病毒感染调节剂，但我们发现其中许多基因确实会影响 IAV 的复制。此外，在几种情况下，特异性抑制 IAV 诱导的剪接模式也会减弱病毒感染。我们进一步表明，IAV 诱导的剪接事件中约有四分之一受到 hnRNP K 的调控，hnRNP K 是一种宿主蛋白，对于 IAV M 转录物在核斑中的有效剪接是必需的。最后，我们发现 IAV 感染后核斑中 hnRNP K 的增加，这可能会改变 hnRNP K 对宿主转录物的可及性，从而导致宿主剪接变化的程序，促进 IAV 的复制。
