Cargando…

Identification and characterization of host proteins bound to dengue virus 3′ UTR reveal an antiviral role for quaking proteins

The four dengue viruses (DENV1-4) are rapidly reemerging infectious RNA viruses. These positive-strand viral genomes contain structured 3′ untranslated regions (UTRs) that interact with various host RNA binding proteins (RBPs). These RBPs are functionally important in viral replication, pathogenesis...

Descripción completa

Detalles Bibliográficos
Autores principales: Liao, Kuo-Chieh, Chuo, Vanessa, Ng, Wy Ching, Neo, Suat Peng, Pompon, Julien, Gunaratne, Jayantha, Ooi, Eng Eong, Garcia-Blanco, Mariano A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959249/
https://www.ncbi.nlm.nih.gov/pubmed/29572260
http://dx.doi.org/10.1261/rna.064006.117
_version_ 1783324361336291328
author Liao, Kuo-Chieh
Chuo, Vanessa
Ng, Wy Ching
Neo, Suat Peng
Pompon, Julien
Gunaratne, Jayantha
Ooi, Eng Eong
Garcia-Blanco, Mariano A.
author_facet Liao, Kuo-Chieh
Chuo, Vanessa
Ng, Wy Ching
Neo, Suat Peng
Pompon, Julien
Gunaratne, Jayantha
Ooi, Eng Eong
Garcia-Blanco, Mariano A.
author_sort Liao, Kuo-Chieh
collection PubMed
description The four dengue viruses (DENV1-4) are rapidly reemerging infectious RNA viruses. These positive-strand viral genomes contain structured 3′ untranslated regions (UTRs) that interact with various host RNA binding proteins (RBPs). These RBPs are functionally important in viral replication, pathogenesis, and defense against host immune mechanisms. Here, we combined RNA chromatography and quantitative mass spectrometry to identify proteins interacting with DENV1-4 3′ UTRs. As expected, RBPs displayed distinct binding specificity. Among them, we focused on quaking (QKI) because of its preference for the DENV4 3′ UTR (DENV-4/SG/06K2270DK1/2005). RNA immunoprecipitation experiments demonstrated that QKI interacted with DENV4 genomes in infected cells. Moreover, QKI depletion enhanced infectious particle production of DENV4. On the contrary, QKI did not interact with DENV2 3′ UTR, and DENV2 replication was not affected consistently by QKI depletion. Next, we mapped the QKI interaction site and identified a QKI response element (QRE) in DENV4 3′ UTR. Interestingly, removal of QRE from DENV4 3′ UTR abolished this interaction and increased DENV4 viral particle production. Introduction of the QRE to DENV2 3′ UTR led to QKI binding and reduced DENV2 infectious particle production. Finally, reporter assays suggest that QKI reduced translation efficiency of viral RNA. Our work describes a novel function of QKI in restricting viral replication.
format Online
Article
Text
id pubmed-5959249
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Cold Spring Harbor Laboratory Press
record_format MEDLINE/PubMed
spelling pubmed-59592492018-06-01 Identification and characterization of host proteins bound to dengue virus 3′ UTR reveal an antiviral role for quaking proteins Liao, Kuo-Chieh Chuo, Vanessa Ng, Wy Ching Neo, Suat Peng Pompon, Julien Gunaratne, Jayantha Ooi, Eng Eong Garcia-Blanco, Mariano A. RNA Article The four dengue viruses (DENV1-4) are rapidly reemerging infectious RNA viruses. These positive-strand viral genomes contain structured 3′ untranslated regions (UTRs) that interact with various host RNA binding proteins (RBPs). These RBPs are functionally important in viral replication, pathogenesis, and defense against host immune mechanisms. Here, we combined RNA chromatography and quantitative mass spectrometry to identify proteins interacting with DENV1-4 3′ UTRs. As expected, RBPs displayed distinct binding specificity. Among them, we focused on quaking (QKI) because of its preference for the DENV4 3′ UTR (DENV-4/SG/06K2270DK1/2005). RNA immunoprecipitation experiments demonstrated that QKI interacted with DENV4 genomes in infected cells. Moreover, QKI depletion enhanced infectious particle production of DENV4. On the contrary, QKI did not interact with DENV2 3′ UTR, and DENV2 replication was not affected consistently by QKI depletion. Next, we mapped the QKI interaction site and identified a QKI response element (QRE) in DENV4 3′ UTR. Interestingly, removal of QRE from DENV4 3′ UTR abolished this interaction and increased DENV4 viral particle production. Introduction of the QRE to DENV2 3′ UTR led to QKI binding and reduced DENV2 infectious particle production. Finally, reporter assays suggest that QKI reduced translation efficiency of viral RNA. Our work describes a novel function of QKI in restricting viral replication. Cold Spring Harbor Laboratory Press 2018-06 /pmc/articles/PMC5959249/ /pubmed/29572260 http://dx.doi.org/10.1261/rna.064006.117 Text en © 2018 Liao et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society http://creativecommons.org/licenses/by-nc/4.0/ This article, published in RNA, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Article
Liao, Kuo-Chieh
Chuo, Vanessa
Ng, Wy Ching
Neo, Suat Peng
Pompon, Julien
Gunaratne, Jayantha
Ooi, Eng Eong
Garcia-Blanco, Mariano A.
Identification and characterization of host proteins bound to dengue virus 3′ UTR reveal an antiviral role for quaking proteins
title Identification and characterization of host proteins bound to dengue virus 3′ UTR reveal an antiviral role for quaking proteins
title_full Identification and characterization of host proteins bound to dengue virus 3′ UTR reveal an antiviral role for quaking proteins
title_fullStr Identification and characterization of host proteins bound to dengue virus 3′ UTR reveal an antiviral role for quaking proteins
title_full_unstemmed Identification and characterization of host proteins bound to dengue virus 3′ UTR reveal an antiviral role for quaking proteins
title_short Identification and characterization of host proteins bound to dengue virus 3′ UTR reveal an antiviral role for quaking proteins
title_sort identification and characterization of host proteins bound to dengue virus 3′ utr reveal an antiviral role for quaking proteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5959249/
https://www.ncbi.nlm.nih.gov/pubmed/29572260
http://dx.doi.org/10.1261/rna.064006.117
work_keys_str_mv AT liaokuochieh identificationandcharacterizationofhostproteinsboundtodenguevirus3utrrevealanantiviralroleforquakingproteins
AT chuovanessa identificationandcharacterizationofhostproteinsboundtodenguevirus3utrrevealanantiviralroleforquakingproteins
AT ngwyching identificationandcharacterizationofhostproteinsboundtodenguevirus3utrrevealanantiviralroleforquakingproteins
AT neosuatpeng identificationandcharacterizationofhostproteinsboundtodenguevirus3utrrevealanantiviralroleforquakingproteins
AT pomponjulien identificationandcharacterizationofhostproteinsboundtodenguevirus3utrrevealanantiviralroleforquakingproteins
AT gunaratnejayantha identificationandcharacterizationofhostproteinsboundtodenguevirus3utrrevealanantiviralroleforquakingproteins
AT ooiengeong identificationandcharacterizationofhostproteinsboundtodenguevirus3utrrevealanantiviralroleforquakingproteins
AT garciablancomarianoa identificationandcharacterizationofhostproteinsboundtodenguevirus3utrrevealanantiviralroleforquakingproteins