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      SARS coronavirus E protein forms cation-selective ion channels

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          Abstract

          Severe Acute Respiratory Syndrome (SARS) is caused by a novel coronavirus (SARS-CoV). Coronaviruses including SARS-CoV encode an envelope (E) protein, a small, hydrophobic membrane protein. We report that, in planar lipid bilayers, synthetic peptides corresponding to the SARS-CoV E protein forms ion channels that are more permeable to monovalent cations than to monovalent anions. Affinity-purified polyclonal antibodies recognizing the N-terminal 19 residues of SARS-CoV E protein were used to establish the specificity of channel formation by inhibiting the ion currents generated in the presence of the E protein peptides.

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          Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome

          Christian Drosten, Stephan Günther, Wolfgang Preiser … (2003)
          The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent. Clinical specimens from patients with SARS were searched for unknown viruses with the use of cell cultures and molecular techniques. A novel coronavirus was identified in patients with SARS. The virus was isolated in cell culture, and a sequence 300 nucleotides in length was obtained by a polymerase-chain-reaction (PCR)-based random-amplification procedure. Genetic characterization indicated that the virus is only distantly related to known coronaviruses (identical in 50 to 60 percent of the nucleotide sequence). On the basis of the obtained sequence, conventional and real-time PCR assays for specific and sensitive detection of the novel virus were established. Virus was detected in a variety of clinical specimens from patients with SARS but not in controls. High concentrations of viral RNA of up to 100 million molecules per milliliter were found in sputum. Viral RNA was also detected at extremely low concentrations in plasma during the acute phase and in feces during the late convalescent phase. Infected patients showed seroconversion on the Vero cells in which the virus was isolated. The novel coronavirus might have a role in causing SARS. Copyright 2003 Massachusetts Medical Society
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            A novel coronavirus associated with severe acute respiratory syndrome.

            Thomas G Ksiazek, Dean Erdman, Cynthia Goldsmith … (2003)
            A worldwide outbreak of severe acute respiratory syndrome (SARS) has been associated with exposures originating from a single ill health care worker from Guangdong Province, China. We conducted studies to identify the etiologic agent of this outbreak. We received clinical specimens from patients in seven countries and tested them, using virus-isolation techniques, electron-microscopical and histologic studies, and molecular and serologic assays, in an attempt to identify a wide range of potential pathogens. None of the previously described respiratory pathogens were consistently identified. However, a novel coronavirus was isolated from patients who met the case definition of SARS. Cytopathological features were noted in Vero E6 cells inoculated with a throat-swab specimen. Electron-microscopical examination revealed ultrastructural features characteristic of coronaviruses. Immunohistochemical and immunofluorescence staining revealed reactivity with group I coronavirus polyclonal antibodies. Consensus coronavirus primers designed to amplify a fragment of the polymerase gene by reverse transcription-polymerase chain reaction (RT-PCR) were used to obtain a sequence that clearly identified the isolate as a unique coronavirus only distantly related to previously sequenced coronaviruses. With specific diagnostic RT-PCR primers we identified several identical nucleotide sequences in 12 patients from several locations, a finding consistent with a point-source outbreak. Indirect fluorescence antibody tests and enzyme-linked immunosorbent assays made with the new isolate have been used to demonstrate a virus-specific serologic response. This virus may never before have circulated in the U.S. population. A novel coronavirus is associated with this outbreak, and the evidence indicates that this virus has an etiologic role in SARS. Because of the death of Dr. Carlo Urbani, we propose that our first isolate be named the Urbani strain of SARS-associated coronavirus. Copyright 2003 Massachusetts Medical Society
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              Coronavirus as a possible cause of severe acute respiratory syndrome.

              V Cheng, A. Yung, J. S. Malik Peiris … (2003)
              An outbreak of severe acute respiratory syndrome (SARS) has been reported in Hong Kong. We investigated the viral cause and clinical presentation among 50 patients. We analysed case notes and microbiological findings for 50 patients with SARS, representing more than five separate epidemiologically linked transmission clusters. We defined the clinical presentation and risk factors associated with severe disease and investigated the causal agents by chest radiography and laboratory testing of nasopharyngeal aspirates and sera samples. We compared the laboratory findings with those submitted for microbiological investigation of other diseases from patients whose identity was masked. Patients' age ranged from 23 to 74 years. Fever, chills, myalgia, and cough were the most frequent complaints. When compared with chest radiographic changes, respiratory symptoms and auscultatory findings were disproportionally mild. Patients who were household contacts of other infected people and had older age, lymphopenia, and liver dysfunction were associated with severe disease. A virus belonging to the family Coronaviridae was isolated from two patients. By use of serological and reverse-transcriptase PCR specific for this virus, 45 of 50 patients with SARS, but no controls, had evidence of infection with this virus. A coronavirus was isolated from patients with SARS that might be the primary agent associated with this disease. Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.
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                Author and article information

                Contributors
                Lauren Wilson
                Journal
                Journal ID (nlm-ta): Virology
                Journal ID (iso-abbrev): Virology
                Title: Virology
                Publisher: Elsevier Inc.
                ISSN (Print): 0042-6822
                ISSN (Electronic): 1096-0341
                Publication date PMC-release: 2 November 2004
                Publication date (Print): 5 December 2004
                Publication date (Electronic): 2 November 2004
                Volume: 330
                Issue: 1
                Pages: 322-331
                Affiliations
                [a ]Medical School, Frank Fenner Building 42, ANU, Canberra, ACT 2601, Australia
                [b ]Biotron Ltd, Innovations Building, ANU, Canberra, ACT 2601, Australia
                [c ]John Curtin School of Medical Research, ANU, Canberra, ACT 2601, Australia
                Author notes
                [* ]Corresponding author. Biotron Ltd, LPO Box A315, Canberra, ACT 2601, Australia. Fax: +61 2 6125 8070. lwilson@ 123456biotron.com.au
                Article
                Publisher ID: S0042-6822(04)00644-0
                DOI: 10.1016/j.virol.2004.09.033
                PMC ID: 7111769
                PubMed ID: 15527857
                SO-VID: 48eb8376-1732-431a-bbfc-b2ead0fe71d6
                Copyright © Copyright © 2004 Elsevier Inc. All rights reserved.
                License:

                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.

                History
                Date received : 25 June 2004
                Date revision received : 27 July 2004
                Date accepted : 26 September 2004
                Categories
                Subject: Article

                ScienceOpen disciplines: Microbiology & Virology
                Keywords: severe acute respiratory syndrome (sars),coronavirus,budding,e protein,ion channel,conductance,vpu,hydrophobic,monovalent cation,mouse hepatitis virus (mhv)
                Data availability:
                ScienceOpen disciplines: Microbiology & Virology
                Keywords: severe acute respiratory syndrome (sars), coronavirus, budding, e protein, ion channel, conductance, vpu, hydrophobic, monovalent cation, mouse hepatitis virus (mhv)

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