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PolyC-Binding Protein 1 Interacts with 5′-Untranslated Region of Enterovirus 71 RNA in Membrane-Associated Complex to Facilitate Viral Replication
Enterovirus 71 (EV71) is one causative agent of hand, foot, and mouth disease (HFMD), which may lead to severe neurological disorders and mortality in children. EV71 genome is a positive single-stranded RNA containing a single open reading frame (ORF) flanked by 5′-untranslated region (5′UTR) and 3′...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906175/ https://www.ncbi.nlm.nih.gov/pubmed/24489926 http://dx.doi.org/10.1371/journal.pone.0087491 |
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author | Luo, Zhen Dong, Xingchen Li, Youxing Zhang, Qi Kim, Cholho Song, Yu Kang, Lei Liu, Yingle Wu, Kailang Wu, Jianguo |
author_facet | Luo, Zhen Dong, Xingchen Li, Youxing Zhang, Qi Kim, Cholho Song, Yu Kang, Lei Liu, Yingle Wu, Kailang Wu, Jianguo |
author_sort | Luo, Zhen |
collection | PubMed |
description | Enterovirus 71 (EV71) is one causative agent of hand, foot, and mouth disease (HFMD), which may lead to severe neurological disorders and mortality in children. EV71 genome is a positive single-stranded RNA containing a single open reading frame (ORF) flanked by 5′-untranslated region (5′UTR) and 3′UTR. The 5′UTR is fundamentally important for virus replication by interacting with cellular proteins. Here, we revealed that poly(C)-binding protein 1 (PCBP1) specifically binds to the 5′UTR of EV71. Detailed studies indicated that the RNA-binding K-homologous 1 (KH1) domain of PCBP1 is responsible for its binding to the stem-loop I and IV of EV71 5′UTR. Interestingly, we revealed that PCBP1 is distributed in the nucleus and cytoplasm of uninfected cells, but mainly localized in the cytoplasm of EV71-infected cells due to interaction and co-localization with the viral RNA. Furthermore, sub-cellular distribution analysis showed that PCBP1 is located in ER-derived membrane, in where virus replication occurred in the cytoplasm of EV71-infected cells, suggesting PCBP1 is recruited in a membrane-associated replication complex. In addition, we found that the binding of PCBP1 to 5′UTR resulted in enhancing EV71 viral protein expression and virus production so as to facilitate viral replication. Thus, we revealed a novel mechanism in which PCBP1 as a positive regulator involved in regulation of EV71 replication in the host specialized membrane-associated replication complex, which provides an insight into cellular factors involved in EV71 replication. |
format | Online Article Text |
id | pubmed-3906175 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-39061752014-01-31 PolyC-Binding Protein 1 Interacts with 5′-Untranslated Region of Enterovirus 71 RNA in Membrane-Associated Complex to Facilitate Viral Replication Luo, Zhen Dong, Xingchen Li, Youxing Zhang, Qi Kim, Cholho Song, Yu Kang, Lei Liu, Yingle Wu, Kailang Wu, Jianguo PLoS One Research Article Enterovirus 71 (EV71) is one causative agent of hand, foot, and mouth disease (HFMD), which may lead to severe neurological disorders and mortality in children. EV71 genome is a positive single-stranded RNA containing a single open reading frame (ORF) flanked by 5′-untranslated region (5′UTR) and 3′UTR. The 5′UTR is fundamentally important for virus replication by interacting with cellular proteins. Here, we revealed that poly(C)-binding protein 1 (PCBP1) specifically binds to the 5′UTR of EV71. Detailed studies indicated that the RNA-binding K-homologous 1 (KH1) domain of PCBP1 is responsible for its binding to the stem-loop I and IV of EV71 5′UTR. Interestingly, we revealed that PCBP1 is distributed in the nucleus and cytoplasm of uninfected cells, but mainly localized in the cytoplasm of EV71-infected cells due to interaction and co-localization with the viral RNA. Furthermore, sub-cellular distribution analysis showed that PCBP1 is located in ER-derived membrane, in where virus replication occurred in the cytoplasm of EV71-infected cells, suggesting PCBP1 is recruited in a membrane-associated replication complex. In addition, we found that the binding of PCBP1 to 5′UTR resulted in enhancing EV71 viral protein expression and virus production so as to facilitate viral replication. Thus, we revealed a novel mechanism in which PCBP1 as a positive regulator involved in regulation of EV71 replication in the host specialized membrane-associated replication complex, which provides an insight into cellular factors involved in EV71 replication. Public Library of Science 2014-01-29 /pmc/articles/PMC3906175/ /pubmed/24489926 http://dx.doi.org/10.1371/journal.pone.0087491 Text en © 2014 Luo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Luo, Zhen Dong, Xingchen Li, Youxing Zhang, Qi Kim, Cholho Song, Yu Kang, Lei Liu, Yingle Wu, Kailang Wu, Jianguo PolyC-Binding Protein 1 Interacts with 5′-Untranslated Region of Enterovirus 71 RNA in Membrane-Associated Complex to Facilitate Viral Replication |
title | PolyC-Binding Protein 1 Interacts with 5′-Untranslated Region of Enterovirus 71 RNA in Membrane-Associated Complex to Facilitate Viral Replication |
title_full | PolyC-Binding Protein 1 Interacts with 5′-Untranslated Region of Enterovirus 71 RNA in Membrane-Associated Complex to Facilitate Viral Replication |
title_fullStr | PolyC-Binding Protein 1 Interacts with 5′-Untranslated Region of Enterovirus 71 RNA in Membrane-Associated Complex to Facilitate Viral Replication |
title_full_unstemmed | PolyC-Binding Protein 1 Interacts with 5′-Untranslated Region of Enterovirus 71 RNA in Membrane-Associated Complex to Facilitate Viral Replication |
title_short | PolyC-Binding Protein 1 Interacts with 5′-Untranslated Region of Enterovirus 71 RNA in Membrane-Associated Complex to Facilitate Viral Replication |
title_sort | polyc-binding protein 1 interacts with 5′-untranslated region of enterovirus 71 rna in membrane-associated complex to facilitate viral replication |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906175/ https://www.ncbi.nlm.nih.gov/pubmed/24489926 http://dx.doi.org/10.1371/journal.pone.0087491 |
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