title: The ORF4a protein of human coronavirus 229E functions as a viroporin that regulates viral production.
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 Xenopus 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(+) 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.
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China; Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Ronghua
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lv
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Yu
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Shiqi
authors.initials: S
authors.lastname: Xie
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.affiliation: Goethe-University Frankfurt, Institute for Biophysics, Max-von-Laue-Str. 1, D-60438 Frankfurt am Main, Germany; Shanghai Research Center for Acupuncture and Meridian, 199 Guoshoujing Road, Shanghai 201023, China.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schwarz
authors.affiliation: Jiangsu Key Laboratory of Infection and Immunity, Institutes of Biology and Medical Sciences, Soochow University, Suzhou 215123, China. Electronic address: sdxiongfd@126.com.
authors.forename: Sidong
authors.initials: S
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China; State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China. Electronic address: bsun@sibs.ac.cn.
authors.forename: Bing
authors.initials: B
authors.lastname: Sun
mesh_terms: D000595:Amino Acid Sequence; D028941:Coronavirus 229E, Human / Q000737:chemistry / Q000502:physiology*; D057809:HEK293 Cells; D006801:Humans; D008969:Molecular Sequence Data; D055503:Protein Multimerization; D014763:Viral Matrix Proteins / Q000737:chemistry / Q000502:physiology*
chemical_list: D014763:Viral Matrix Proteins
keywords: HCoV-229E; Homo-oligomers; Ion channel; ORF4a; Viroporin
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