A second open reading frame in human enterovirus determines viral replication in intestinal epithelial cells

Haoran Guo, Yan Li, Guanchen Liu, Yunhe Jiang, Siyu Shen, Ran Bi, Honglan Huang, Tong Cheng, Chunxi Wang and Wei Wei ()
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Haoran Guo: Jilin University
Yan Li: Jilin University
Guanchen Liu: Jilin University
Yunhe Jiang: Jilin University
Siyu Shen: Jilin University
Ran Bi: Jilin University
Honglan Huang: Jilin University
Tong Cheng: Xiamen University
Chunxi Wang: Jilin University
Wei Wei: Jilin University

Nature Communications, 2019, vol. 10, issue 1, 1-9

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-12040-9

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