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      Coronavirus nonstructural protein 1: Common and distinct functions in the regulation of host and viral gene expression

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          Highlights

          • Novel strategies to inhibit host gene expression by coronavirus nonstructural protein 1.

          • Summarizes the conserved and divergent functions of Alpha and Betacoronavirus nsp1.

          • Provides a mechanistic insight into the unique properties of SARS coronavirus nsp1.

          Abstract

          The recent emergence of two highly pathogenic human coronaviruses (CoVs), severe acute respiratory syndrome CoV and Middle East respiratory syndrome CoV, has ignited a strong interest in the identification of viral factors that determine the virulence and pathogenesis of CoVs. The nonstructural protein 1 (nsp1) of CoVs has attracted considerable attention in this regard as a potential virulence factor and a target for CoV vaccine development because of accumulating evidence that point to its role in the downregulation of host innate immune responses to CoV infection. Studies have revealed both functional conservation and mechanistic divergence among the nsp1 of different mammalian CoVs in perturbing host gene expression and antiviral responses. This review summarizes the current knowledge about the biological functions of CoV nsp1 that provides an insight into the novel strategies utilized by this viral protein to modulate host and viral gene expression during CoV infection.

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          Most cited references56

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          Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia.

          A previously unknown coronavirus was isolated from the sputum of a 60-year-old man who presented with acute pneumonia and subsequent renal failure with a fatal outcome in Saudi Arabia. The virus (called HCoV-EMC) replicated readily in cell culture, producing cytopathic effects of rounding, detachment, and syncytium formation. The virus represents a novel betacoronavirus species. The closest known relatives are bat coronaviruses HKU4 and HKU5. Here, the clinical data, virus isolation, and molecular identification are presented. The clinical picture was remarkably similar to that of the severe acute respiratory syndrome (SARS) outbreak in 2003 and reminds us that animal coronaviruses can cause severe disease in humans.
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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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                Author and article information

                Contributors
                Journal
                Virus Res
                Virus Res
                Virus Research
                Elsevier B.V.
                0168-1702
                1872-7492
                26 November 2014
                16 April 2015
                26 November 2014
                : 202
                : 89-100
                Affiliations
                [a ]Department of Microbiology and Immunology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555-1019, United States
                [b ]Department of Pathology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555-1019, United States
                Author notes
                [* ]Corresponding author. Tel.: +1 409 772 8172; fax: +1 409 772 5065. krnaraya@ 123456utmb.edu
                [** ]Corresponding author. Tel.: +1 409 772 2323; fax: +1 409 772 5065. shmakino@ 123456utmb.edu
                [1]

                These authors contributed equally to this study.

                [2]

                Tel.: +1 409 772 8172.

                Article
                S0168-1702(14)00494-8
                10.1016/j.virusres.2014.11.019
                4444399
                25432065
                dc6f1d1a-ac3c-4b28-94f1-4d4577ddb691
                Copyright © 2014 Elsevier B.V. All rights reserved.

                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
                Categories
                Article

                Microbiology & Virology
                rna viruses,coronavirus,nsp1,translation inhibition,mrna cleavage,sars
                Microbiology & Virology
                rna viruses, coronavirus, nsp1, translation inhibition, mrna cleavage, sars

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