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      Tissue and cellular tropism of the coronavirus associated with severe acute respiratory syndrome: an in‐situ hybridization study of fatal cases

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          Abstract

          Severe acute respiratory syndrome (SARS) is a new human infectious disease with significant morbidity and mortality. The disease has been shown to be associated with a new coronavirus (SARS‐CoV). The clinical and epidemiological aspects of SARS have been described. Moreover, the viral genome of SARS‐CoV has been fully sequenced. However, much of the biological behaviour of the virus is not known and data on the tissue and cellular tropism of SARS‐CoV are limited. In this study, six fatal cases of SARS were investigated for the tissue and cellular tropism of SARS‐CoV using an in‐situ hybridization (ISH) technique. Among all the tissues studied, positive signals were seen in pneumocytes in the lungs and surface enterocytes in the small bowel. Infected pneumocytes were further confirmed by immunofluorescence–fluorescence in‐situ hybridization (FISH) analysis. These results provide important information concerning the tissue tropism of SARS‐CoV, which is distinct from previously identified human coronaviruses, and suggest the possible involvement of novel receptors in this infection. Whereas the lung pathology was dominated by diffuse alveolar damage, the gut was relatively intact. These findings indicated that tissue responses to SARS‐CoV infection are distinct in different organs. Copyright © 2004 John Wiley & Sons, Ltd.

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          Most cited references9

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

          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.

            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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              Characterization of a novel coronavirus associated with severe acute respiratory syndrome.

              P Rota (2003)
              In March 2003, a novel coronavirus (SARS-CoV) was discovered in association with cases of severe acute respiratory syndrome (SARS). The sequence of the complete genome of SARS-CoV was determined, and the initial characterization of the viral genome is presented in this report. The genome of SARS-CoV is 29,727 nucleotides in length and has 11 open reading frames, and its genome organization is similar to that of other coronaviruses. Phylogenetic analyses and sequence comparisons showed that SARS-CoV is not closely related to any of the previously characterized coronaviruses.
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                Author and article information

                Contributors
                kfto@cuhk.edu.hk
                Journal
                J Pathol
                J. Pathol
                10.1002/(ISSN)1096-9896
                PATH
                The Journal of Pathology
                John Wiley & Sons, Ltd. (Chichester, UK )
                0022-3417
                1096-9896
                19 January 2004
                February 2004
                : 202
                : 2 ( doiID: 10.1002/path.v202:2 )
                : 157-163
                Affiliations
                [ 1 ]Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China
                [ 2 ]Department of Microbiology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong SAR, China
                [ 3 ]Department of Chemical Pathology, The Chinese University of Hong Kong, Hong Kong SAR, China
                Author notes
                [*] [* ]Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, 30‐32 Ngan Shing Street, Shatin, NT, Hong Kong SAR, China.
                Article
                PATH1510
                10.1002/path.1510
                7167900
                14743497
                3b53ae0b-4e80-4578-ae53-0b0342922260
                Copyright © 2004 John Wiley & Sons, Ltd.

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 21 July 2003
                : 06 September 2003
                : 28 October 2003
                Page count
                Figures: 5, Tables: 1, References: 23, Pages: 7
                Categories
                Original Paper
                Original Papers
                Custom metadata
                2.0
                February 2004
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:15.04.2020

                Pathology
                severe acute respiratory syndrome (sars),coronavirus,viral tropism
                Pathology
                severe acute respiratory syndrome (sars), coronavirus, viral tropism

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