The ORF4a protein of human coronavirus 229E functions as a viroporin that regulates viral production☆
Identifieur interne : 000E31 ( Pmc/Curation ); précédent : 000E30; suivant : 000E32The ORF4a protein of human coronavirus 229E functions as a viroporin that regulates viral production☆
Auteurs : Ronghua Zhang [République populaire de Chine] ; Kai Wang [République populaire de Chine] ; Wei Lv [République populaire de Chine] ; Wenjing Yu [République populaire de Chine] ; Shiqi Xie [République populaire de Chine] ; Ke Xu [République populaire de Chine] ; Wolfgang Schwarz [Allemagne, République populaire de Chine] ; Sidong Xiong [République populaire de Chine] ; Bing Sun [République populaire de Chine]Source :
- Biochimica et Biophysica Acta. Biomembranes [ 0005-2736 ] ; 2013.
Abstract
In addition to a set of canonical genes, coronaviruses encode additional accessory proteins. A locus located between the spike and envelope genes is conserved in all coronaviruses and contains a complete or truncated open reading frame (ORF). Previously, we demonstrated that this locus, which contains the gene for accessory protein 3a from severe acute respiratory syndrome coronavirus (SARS-CoV), encodes a protein that forms ion channels and regulates virus release. In the current study, we explored whether the ORF4a protein of HCoV-229E has similar functions. Our findings revealed that the ORF4a proteins were expressed in infected cells and localized at the endoplasmic reticulum/Golgi intermediate compartment (ERGIC). The ORF4a proteins formed homo-oligomers through disulfide bridges and possessed ion channel activity in both
Url:
DOI: 10.1016/j.bbamem.2013.07.025
PubMed: 23906728
PubMed Central: 7094429
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<front><div type="abstract" xml:lang="en"><p>In addition to a set of canonical genes, coronaviruses encode additional accessory proteins. A locus located between the spike and envelope genes is conserved in all coronaviruses and contains a complete or truncated open reading frame (ORF). Previously, we demonstrated that this locus, which contains the gene for accessory protein 3a from severe acute respiratory syndrome coronavirus (SARS-CoV), encodes a protein that forms ion channels and regulates virus release. In the current study, we explored whether the ORF4a protein of HCoV-229E has similar functions. Our findings revealed that the ORF4a proteins were expressed in infected cells and localized at the endoplasmic reticulum/Golgi intermediate compartment (ERGIC). The ORF4a proteins formed homo-oligomers through disulfide bridges and possessed ion channel activity in both <italic>Xenopus</italic>
oocytes and yeast. Based on the measurement of conductance to different monovalent cations, the ORF4a was suggested to form a non-selective channel for monovalent cations, although Li<sup>+</sup>
partially reduced the inward current. Furthermore, viral production decreased when the ORF4a protein expression was suppressed by siRNA in infected cells. Collectively, this evidence indicates that the HCoV-229E ORF4a protein is functionally analogous to the SARS-CoV 3a protein, which also acts as a viroporin that regulates virus production. This article is part of a Special Issue entitled: Viral Membrane Proteins — Channels for Cellular Networking.</p>
</div>
</front>
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<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Biochim Biophys Acta Biomembr</journal-id>
<journal-id journal-id-type="iso-abbrev">Biochim Biophys Acta Biomembr</journal-id>
<journal-title-group><journal-title>Biochimica et Biophysica Acta. Biomembranes</journal-title>
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<issn pub-type="ppub">0005-2736</issn>
<issn pub-type="epub">1879-2642</issn>
<publisher><publisher-name>Elsevier B.V.</publisher-name>
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<article-meta><article-id pub-id-type="pmid">23906728</article-id>
<article-id pub-id-type="pmc">7094429</article-id>
<article-id pub-id-type="publisher-id">S0005-2736(13)00271-X</article-id>
<article-id pub-id-type="doi">10.1016/j.bbamem.2013.07.025</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
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</article-categories>
<title-group><article-title>The ORF4a protein of human coronavirus 229E functions as a viroporin that regulates viral production<sup><xref ref-type="fn" rid="d32e1024">☆</xref>
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<given-names>Ronghua</given-names>
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<xref rid="af0005" ref-type="aff">a</xref>
<xref rid="af0010" ref-type="aff">b</xref>
<xref rid="fn0005" ref-type="fn">1</xref>
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<email>sdxiongfd@126.com</email>
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<xref rid="cr0005" ref-type="corresp">⁎</xref>
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<email>bsun@sibs.ac.cn</email>
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<xref rid="cr0010" ref-type="corresp">⁎⁎</xref>
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<aff id="af0005"><label>a</label>
Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China</aff>
<aff id="af0010"><label>b</label>
Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China</aff>
<aff id="af0015"><label>c</label>
Goethe-University Frankfurt, Institute for Biophysics, Max-von-Laue-Str. 1, D-60438 Frankfurt am Main, Germany</aff>
<aff id="af0020"><label>d</label>
Shanghai Research Center for Acupuncture and Meridian, 199 Guoshoujing Road, Shanghai 201023, China</aff>
<aff id="af0025"><label>e</label>
State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China</aff>
<author-notes><corresp id="cr0005"><label>⁎</label>
Corresponding author. Tel./fax: + 86 512 65881255. <email>sdxiongfd@126.com</email>
</corresp>
<corresp id="cr0010"><label>⁎⁎</label>
Correspondence to: B. Sun, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 225 South Chongqing Road, Shanghai 200025, China. Tel.: + 86 21 63851927; fax: + 86 21 63843571. <email>bsun@sibs.ac.cn</email>
</corresp>
<fn id="fn0005"><label>1</label>
<p id="np0010">Authors who contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="pmc-release"><day>29</day>
<month>7</month>
<year>2013</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><month>4</month>
<year>2014</year>
</pub-date>
<pub-date pub-type="epub"><day>29</day>
<month>7</month>
<year>2013</year>
</pub-date>
<volume>1838</volume>
<issue>4</issue>
<fpage>1088</fpage>
<lpage>1095</lpage>
<history><date date-type="received"><day>19</day>
<month>3</month>
<year>2013</year>
</date>
<date date-type="rev-recd"><day>12</day>
<month>7</month>
<year>2013</year>
</date>
<date date-type="accepted"><day>18</day>
<month>7</month>
<year>2013</year>
</date>
</history>
<permissions><copyright-statement>Copyright © 2013 Elsevier B.V. All rights reserved.</copyright-statement>
<copyright-year>2013</copyright-year>
<copyright-holder>Elsevier B.V.</copyright-holder>
<license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p>
</license>
</permissions>
<abstract id="ab0005"><p>In addition to a set of canonical genes, coronaviruses encode additional accessory proteins. A locus located between the spike and envelope genes is conserved in all coronaviruses and contains a complete or truncated open reading frame (ORF). Previously, we demonstrated that this locus, which contains the gene for accessory protein 3a from severe acute respiratory syndrome coronavirus (SARS-CoV), encodes a protein that forms ion channels and regulates virus release. In the current study, we explored whether the ORF4a protein of HCoV-229E has similar functions. Our findings revealed that the ORF4a proteins were expressed in infected cells and localized at the endoplasmic reticulum/Golgi intermediate compartment (ERGIC). The ORF4a proteins formed homo-oligomers through disulfide bridges and possessed ion channel activity in both <italic>Xenopus</italic>
oocytes and yeast. Based on the measurement of conductance to different monovalent cations, the ORF4a was suggested to form a non-selective channel for monovalent cations, although Li<sup>+</sup>
partially reduced the inward current. Furthermore, viral production decreased when the ORF4a protein expression was suppressed by siRNA in infected cells. Collectively, this evidence indicates that the HCoV-229E ORF4a protein is functionally analogous to the SARS-CoV 3a protein, which also acts as a viroporin that regulates virus production. This article is part of a Special Issue entitled: Viral Membrane Proteins — Channels for Cellular Networking.</p>
</abstract>
<abstract abstract-type="graphical" id="ab0010"><title>Graphical abstract</title>
<fig id="f0005" position="anchor"><graphic xlink:href="fx1_lrg"></graphic>
</fig>
</abstract>
<abstract abstract-type="author-highlights" id="ab0015"><title>Highlights</title>
<p><list list-type="simple" id="l0005"><list-item id="u0005"><label>•</label>
<p id="p0125">HCoV-229E ORF4a protein is expressed in the infected Huh-7 cells and localized in the ERGIC.</p>
</list-item>
<list-item id="u0010"><label>•</label>
<p id="p0130">ORF4a forms homo-oligomers and serves as ion channels in both <italic>Xenopus</italic>
oocytes and yeast.</p>
</list-item>
<list-item id="u0015"><label>•</label>
<p id="p0135">ORF4a protein is a non-selective channel for monovalent cations.</p>
</list-item>
<list-item id="u0020"><label>•</label>
<p id="p0140">HCoV-229E ORF4a protein acts as viroporins to regulate the virus production.</p>
</list-item>
</list>
</p>
</abstract>
<kwd-group id="ks0005"><title>Abbreviations</title>
<kwd>CoV, coronavirus</kwd>
<kwd>HCoV, human coronavirus</kwd>
<kwd>SARS-CoV, severe acute respiratory syndrome coronavirus</kwd>
<kwd>ORF, open reading frame</kwd>
<kwd>PEDV, porcine epidemic diarrhea virus</kwd>
<kwd>TGEV, transmissible gastroenteritis virus</kwd>
<kwd>ERGIC, endoplasmic reticulum/Golgi intermediate compartment</kwd>
<kwd>β-ME, β-mercaptoethanol</kwd>
<kwd>TMD, transmembrane domain</kwd>
<kwd>cRNA, complementary RNA</kwd>
<kwd>ORi, oocyte Ringer's-like solution</kwd>
<kwd>TEVC, two-electrode voltage clamp</kwd>
<kwd>MOI, multiplicity of infection</kwd>
<kwd>TCID<sub>50</sub>
, 50% tissue culture infective dose</kwd>
</kwd-group>
<kwd-group id="ks0010"><title>Keywords</title>
<kwd>HCoV-229E</kwd>
<kwd>ORF4a</kwd>
<kwd>Homo-oligomers</kwd>
<kwd>Ion channel</kwd>
<kwd>Viroporin</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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