Viral-induced alternative splicing of host genes promotes influenza replication.
Viral-induced alternative splicing of host genes promotes influenza replication.
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DOI：
10.7554/elife.55500
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发表时间：
2020-12-03
期刊：
影响因子：
7.7
通讯作者：
Lynch KW
中科院分区：
文献类型：
--
作者：
Thompson MG;Dittmar M;Mallory MJ;Bhat P;Ferretti MB;Fontoura BM;Cherry S;Lynch KW
病毒感染诱导许多影响感染结果的宿主基因的表达。在这里，我们发现甲型流感病毒（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。尽管这些剪接调节基因并未富集病毒感染的典型调节因子，但我们发现其中许多基因确实影响 IAV 的复制。此外，在一些情况下，对 IAV 诱导的剪接模式的特异性抑制也能减弱病毒感染。我们进一步表明，大约四分之一的 IAV 诱导的剪接事件是由 hnRNP K 调节的，hnRNP K 是 IAV M 转录物在核斑点中有效剪接所需的宿主蛋白。最后，我们发现 IAV 感染后核斑点中 hnRNP K 增加，这可能会改变宿主转录本的 hnRNP K 的可及性，从而导致促进 IAV 复制的宿主剪接变化程序。
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.