Key Laboratory of Organ Regeneration and Transplantation of Ministry of Education, Institute of Translational Medicine, First Hospital, Jilin University, Changchun, Jilin, 130021, China.
Institute of Virology and AIDS Research, First Hospital, Jilin University, Changchun, Jilin, 130021, China.
Nat Commun. 2019 Sep 6;10(1):4066. doi: 10.1038/s41467-019-12040-9.
Human enteroviruses (HEVs) of the family Picornaviridae, 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.
人肠道病毒（HEV）属于小 RNA 病毒科，是无包膜的 RNA 病毒，广泛存在于世界各地。大多数 EV 蛋白源自由单个开放阅读框（ORF）编码的病毒多蛋白。在这里，我们描述了 HEV 中的第二个 ORF，该 ORF 对病毒肠道感染至关重要。破坏 ORF2p 的表达会降低 EV-A71 在人肠上皮细胞（IEC）中的复制能力。来自不同肠型肠道病毒的 ORF2p 蛋白的异位表达使肠道细胞对 ORF2p 缺失的 EV-A71 和呼吸道肠道病毒 EV-D68 的复制敏感。我们表明，ORF2p 的高度保守 WIGHPV 结构域对 ORF2p 依赖性病毒肠道感染很重要。ORF2p 的表达对于 EV-A71 粒子从 IEC 中的释放是必需的，并且可以通过促进病毒释放来支持 IEC 中 EV-D68 的有效感染。我们的结果表明，ORF2p 是人肠道病毒在 IEC 中复制的决定因素。
