Serveur d'exploration MERS

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Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis

Identifieur interne : 000F72 ( Ncbi/Merge ); précédent : 000F71; suivant : 000F73

Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis

Auteurs : Jean Kaoru Millet ; Gary R. Whittaker

Source :

RBID : PMC:4465284

Descripteurs français

English descriptors

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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Links to Exploration step

PMC:4465284

Le document en format XML

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<term>Host Specificity</term>
<term>Host-Pathogen Interactions</term>
<term>Humans</term>
<term>Peptide Hydrolases (metabolism)</term>
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<term>Spike Glycoprotein, Coronavirus (metabolism)</term>
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<term>Coronaviridae (pathogénicité)</term>
<term>Coronaviridae (physiologie)</term>
<term>Glycoprotéine de spicule des coronavirus (métabolisme)</term>
<term>Humains</term>
<term>Interactions hôte-pathogène</term>
<term>Peptide hydrolases (métabolisme)</term>
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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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<title xml:lang="en">Host cell proteases: Critical determinants of coronavirus tropism and pathogenesis</title>
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<author>
<name sortKey="Whittaker, Gary R" sort="Whittaker, Gary R" uniqKey="Whittaker G" first="Gary R." last="Whittaker">Gary R. Whittaker</name>
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<idno type="doi">10.1016/j.virusres.2014.11.021</idno>
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<name sortKey="Millet, Jean Kaoru" sort="Millet, Jean Kaoru" uniqKey="Millet J" first="Jean Kaoru" last="Millet">Jean Kaoru Millet</name>
</author>
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<name sortKey="Whittaker, Gary R" sort="Whittaker, Gary R" uniqKey="Whittaker G" first="Gary R." last="Whittaker">Gary R. Whittaker</name>
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<series>
<title level="j">Virus Research</title>
<idno type="ISSN">0168-1702</idno>
<idno type="eISSN">1872-7492</idno>
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<date when="2014">2014</date>
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<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>
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</p>
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<name sortKey="Rohn, M" uniqKey="Rohn M">M. Rohn</name>
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<name sortKey="Mcgregor, G P" uniqKey="Mcgregor G">G.P. McGregor</name>
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<name sortKey="Blazejewska, P" uniqKey="Blazejewska P">P. Blazejewska</name>
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<name sortKey="Moldenhauer, A S" uniqKey="Moldenhauer A">A.-S. Moldenhauer</name>
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<name sortKey="Welsch, K" uniqKey="Welsch K">K. Welsch</name>
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<name sortKey="Nehlmeier, I" uniqKey="Nehlmeier I">I. Nehlmeier</name>
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<nlm:affiliation>Department of Microbiology and Immunology, Cornell University, C4 127 VMC, Ithaca, NY 14853, United States.</nlm:affiliation>
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<wicri:regionArea>Department of Microbiology and Immunology, Cornell University, C4 127 VMC, Ithaca, NY 14853</wicri:regionArea>
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<nlm:affiliation>Department of Microbiology and Immunology, Cornell University, C4 127 VMC, Ithaca, NY 14853, United States. Electronic address: grw7@cornell.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Cornell University, C4 127 VMC, Ithaca, NY 14853</wicri:regionArea>
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<name sortKey="Millet, Jean Kaoru" sort="Millet, Jean Kaoru" uniqKey="Millet J" first="Jean Kaoru" last="Millet">Jean Kaoru Millet</name>
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<nlm:affiliation>Department of Microbiology and Immunology, Cornell University, C4 127 VMC, Ithaca, NY 14853, United States.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Cornell University, C4 127 VMC, Ithaca, NY 14853</wicri:regionArea>
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<region type="state">État de New York</region>
<settlement type="city">Ithaca (New York)</settlement>
</placeName>
<orgName type="university">Université Cornell</orgName>
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</author>
<author>
<name sortKey="Whittaker, Gary R" sort="Whittaker, Gary R" uniqKey="Whittaker G" first="Gary R" last="Whittaker">Gary R. Whittaker</name>
<affiliation wicri:level="4">
<nlm:affiliation>Department of Microbiology and Immunology, Cornell University, C4 127 VMC, Ithaca, NY 14853, United States. Electronic address: grw7@cornell.edu.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Microbiology and Immunology, Cornell University, C4 127 VMC, Ithaca, NY 14853</wicri:regionArea>
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<region type="state">État de New York</region>
<settlement type="city">Ithaca (New York)</settlement>
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<title level="j">Virus research</title>
<idno type="eISSN">1872-7492</idno>
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<date when="2015" type="published">2015</date>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Coronaviridae (pathogenicity)</term>
<term>Coronaviridae (physiology)</term>
<term>Host Specificity</term>
<term>Host-Pathogen Interactions</term>
<term>Humans</term>
<term>Peptide Hydrolases (metabolism)</term>
<term>Proteolysis</term>
<term>Spike Glycoprotein, Coronavirus (metabolism)</term>
<term>Viral Tropism</term>
</keywords>
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<term>Coronaviridae (pathogénicité)</term>
<term>Coronaviridae (physiologie)</term>
<term>Glycoprotéine de spicule des coronavirus (métabolisme)</term>
<term>Humains</term>
<term>Interactions hôte-pathogène</term>
<term>Peptide hydrolases (métabolisme)</term>
<term>Protéolyse</term>
<term>Spécificité d'hôte</term>
<term>Tropisme viral</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en">
<term>Peptide Hydrolases</term>
<term>Spike Glycoprotein, Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr">
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Peptide hydrolases</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en">
<term>Coronaviridae</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr">
<term>Coronaviridae</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr">
<term>Coronaviridae</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en">
<term>Coronaviridae</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Host Specificity</term>
<term>Host-Pathogen Interactions</term>
<term>Humans</term>
<term>Proteolysis</term>
<term>Viral Tropism</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Humains</term>
<term>Interactions hôte-pathogène</term>
<term>Protéolyse</term>
<term>Spécificité d'hôte</term>
<term>Tropisme viral</term>
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<front>
<div type="abstract" xml:lang="en">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. </div>
</front>
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