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Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis

Identifieur interne : 001603 ( Pmc/Curation ); précédent : 001602; suivant : 001604

Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis

Auteurs : Jean Kaoru Millet ; Gary R. Whittaker

Source :

RBID : PMC:4465284

Abstract

Highlights

Coronavirus spike proteins can be cleaved by a multitude of host cell proteases.

Proteolytic activation of spike is a crucial step to activate its fusogenicity.

The spike protein can be cleaved at multiple sites.

Modulation of spike cleavage can have profound effects on tropism and pathogenesis.


Url:
DOI: 10.1016/j.virusres.2014.11.021
PubMed: 25445340
PubMed Central: 4465284

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PMC:4465284

Le document en format XML

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<p id="par0005">Coronavirus spike proteins can be cleaved by a multitude of host cell proteases.</p>
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<p id="par0010">Proteolytic activation of spike is a crucial step to activate its fusogenicity.</p>
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<p id="par0015">The spike protein can be cleaved at multiple sites.</p>
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<p id="par0020">Modulation of spike cleavage can have profound effects on tropism and pathogenesis.</p>
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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">Virus Res</journal-id>
<journal-id journal-id-type="iso-abbrev">Virus Res</journal-id>
<journal-title-group>
<journal-title>Virus Research</journal-title>
</journal-title-group>
<issn pub-type="ppub">0168-1702</issn>
<issn pub-type="epub">1872-7492</issn>
<publisher>
<publisher-name>Elsevier B.V.</publisher-name>
</publisher>
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<article-meta>
<article-id pub-id-type="pmid">25445340</article-id>
<article-id pub-id-type="pmc">4465284</article-id>
<article-id pub-id-type="publisher-id">S0168-1702(14)00496-1</article-id>
<article-id pub-id-type="doi">10.1016/j.virusres.2014.11.021</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" id="aut0005">
<name>
<surname>Millet</surname>
<given-names>Jean Kaoru</given-names>
</name>
</contrib>
<contrib contrib-type="author" id="aut0010">
<name>
<surname>Whittaker</surname>
<given-names>Gary R.</given-names>
</name>
<email>grw7@cornell.edu</email>
<xref rid="cor0005" ref-type="corresp"></xref>
</contrib>
</contrib-group>
<aff id="aff0005">Department of Microbiology and Immunology, Cornell University, C4 127 VMC, Ithaca, NY 14853, United States</aff>
<author-notes>
<corresp id="cor0005">
<label></label>
Corresponding author. Tel.: +1 607 253 4019.
<email>grw7@cornell.edu</email>
</corresp>
</author-notes>
<pub-date pub-type="pmc-release">
<day>22</day>
<month>11</month>
<year>2014</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">
<day>16</day>
<month>4</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="epub">
<day>22</day>
<month>11</month>
<year>2014</year>
</pub-date>
<volume>202</volume>
<fpage>120</fpage>
<lpage>134</lpage>
<permissions>
<copyright-statement>Copyright © 2014 Elsevier B.V. All rights reserved.</copyright-statement>
<copyright-year>2014</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 abstract-type="author-highlights" id="abs0005">
<title>Highlights</title>
<p>
<list list-type="simple" id="lis0005">
<list-item id="lsti0005">
<label></label>
<p id="par0005">Coronavirus spike proteins can be cleaved by a multitude of host cell proteases.</p>
</list-item>
<list-item id="lsti0010">
<label></label>
<p id="par0010">Proteolytic activation of spike is a crucial step to activate its fusogenicity.</p>
</list-item>
<list-item id="lsti0015">
<label></label>
<p id="par0015">The spike protein can be cleaved at multiple sites.</p>
</list-item>
<list-item id="lsti0020">
<label></label>
<p id="par0020">Modulation of spike cleavage can have profound effects on tropism and pathogenesis.</p>
</list-item>
</list>
</p>
</abstract>
<abstract id="abs0010">
<p>Coronaviruses are a large group of enveloped, single-stranded positive-sense RNA viruses that infect a wide range of avian and mammalian species, including humans. The emergence of deadly human coronaviruses, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle East respiratory syndrome coronavirus (MERS-CoV) have bolstered research in these viral and often zoonotic pathogens. While coronavirus cell and tissue tropism, host range, and pathogenesis are initially controlled by interactions between the spike envelope glycoprotein and host cell receptor, it is becoming increasingly apparent that proteolytic activation of spike by host cell proteases also plays a critical role. Coronavirus spike proteins are the main determinant of entry as they possess both receptor binding and fusion functions. Whereas binding to the host cell receptor is an essential first step in establishing infection, the proteolytic activation step is often critical for the fusion function of spike, as it allows for controlled release of the fusion peptide into target cellular membranes. Coronaviruses have evolved multiple strategies for proteolytic activation of spike, and a large number of host proteases have been shown to proteolytically process the spike protein. These include, but are not limited to, endosomal cathepsins, cell surface transmembrane protease/serine (TMPRSS) proteases, furin, and trypsin. This review focuses on the diversity of strategies coronaviruses have evolved to proteolytically activate their fusion protein during spike protein biosynthesis and the critical entry step of their life cycle, and highlights important findings on how proteolytic activation of coronavirus spike influences tissue and cell tropism, host range and pathogenicity.</p>
</abstract>
<kwd-group id="kwd0005">
<title>Keywords</title>
<kwd>Cleavage activation</kwd>
<kwd>Coronavirus</kwd>
<kwd>Pathogenesis</kwd>
<kwd>Protease</kwd>
<kwd>Spike protein</kwd>
<kwd>Tropism</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>

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