A second open reading frame in human enterovirus determines viral replication in intestinal epithelial cells
A second open reading frame in human enterovirus determines viral replication in intestinal epithelial cells
复制标题
人类肠道病毒的第二个开放阅读框决定病毒在肠上皮细胞中的复制
DOI：
10.1038/s41467-019-12040-9
复制
发表时间：
2019-09-06
影响因子：
16.6
通讯作者：
Wei, Wei
中科院分区：
文献类型：
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作者：
Guo, Haoran;Li, Yan;Wei, Wei
人肠道病毒(HEV)是由非囊膜RNA病毒组成的猪科肠道病毒，在世界范围内普遍存在。大多数EV蛋白来源于由单一开放阅读框架(ORF)编码的病毒多蛋白。在这里，我们描述了HEV中的第二个ORF，它对病毒性肠道感染至关重要。ORF2p的表达中断降低了EV-A71在人肠上皮细胞(IECS)的复制能力。来自不同肠道病毒的ORF2p蛋白的异位表达使肠道细胞对ORF2p缺陷的EV-A71和呼吸道肠道病毒EV-D68的复制敏感。我们发现ORF2p高度保守的WIGHPV结构域对于依赖ORF2p的病毒肠道感染是重要的。ORF2p的表达是EV-A71颗粒从IECS释放所必需的，并且可以通过促进病毒的释放来支持EV-D68在IECS中的生产性感染。我们的结果表明，ORF2p是肠道病毒在IECS中复制的决定因素。
Human enteroviruses (HEVs) of the familyPicornaviridae, which comprises non-enveloped RNA viruses, are ubiquitous worldwide. The majority of EV proteins are derived from viral polyproteins encoded by a single open reading frame (ORF). Here, we characterize a second ORF in HEVs that is crucial for viral intestinal infection. Disruption of ORF2p expression decreases the replication capacity of EV-A71 in human intestinal epithelial cells (IECs). Ectopic expression of ORF2p proteins derived from diverse enteric enteroviruses sensitizes intestinal cells to the replication of ORF2p-defective EV-A71 and respiratory enterovirus EV-D68. We show that the highly conserved WIGHPV domain of ORF2p is important for ORF2p-dependent viral intestinal infection. ORF2p expression is required for EV-A71 particle release from IECs and can support productive EV-D68 infection in IECs by facilitating virus release. Our results indicate that ORF2p is a determining factor for enteric enterovirus replication in IECs.