Adaptive evolution influences the infectious dose of MERS-CoV necessary to achieve severe respiratory disease
Identifieur interne : 001184 ( Pmc/Curation ); précédent : 001183; suivant : 001185Adaptive evolution influences the infectious dose of MERS-CoV necessary to achieve severe respiratory disease
Auteurs : Madeline G. Douglas [États-Unis] ; Jacob F. Kocher [États-Unis] ; Trevor Scobey [États-Unis] ; Ralph S. Baric [États-Unis] ; Adam S. Cockrell [États-Unis]Source :
- Virology [ 0042-6822 ] ; 2017.
Abstract
We recently established a mouse model (288–330+/+) that developed acute respiratory disease resembling human pathology following infection with a high dose (5 × 106 PFU) of mouse-adapted MERS-CoV (icMERSma1). Although this high dose conferred fatal respiratory disease in mice, achieving similar pathology at lower viral doses may more closely reflect naturally acquired infections. Through continued adaptive evolution of icMERSma1 we generated a novel mouse-adapted MERS-CoV (maM35c4) capable of achieving severe respiratory disease at doses between 103 and 105 PFU. Novel mutations were identified in the maM35c4 genome that may be responsible for eliciting etiologies of acute respiratory distress syndrome at 10–1000 fold lower viral doses. Importantly, comparative genetics of the two mouse-adapted MERS strains allowed us to identify specific mutations that remained fixed through an additional 20 cycles of adaptive evolution. Our data indicate that the extent of MERS-CoV adaptation determines the minimal infectious dose required to achieve severe respiratory disease.
Url:
DOI: 10.1016/j.virol.2017.12.006
PubMed: 29277291
PubMed Central: 5869108
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<series><title level="j">Virology</title>
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<front><div type="abstract" xml:lang="en"><p>We recently established a mouse model (288–330<sup>+/+</sup>
) that developed acute respiratory disease resembling human pathology following infection with a high dose (5 × 10<sup>6</sup>
PFU) of mouse-adapted MERS-CoV (icMERSma1). Although this high dose conferred fatal respiratory disease in mice, achieving similar pathology at lower viral doses may more closely reflect naturally acquired infections. Through continued adaptive evolution of icMERSma1 we generated a novel mouse-adapted MERS-CoV (maM35c4) capable of achieving severe respiratory disease at doses between 10<sup>3</sup>
and 10<sup>5</sup>
PFU. Novel mutations were identified in the maM35c4 genome that may be responsible for eliciting etiologies of acute respiratory distress syndrome at 10–1000 fold lower viral doses. Importantly, comparative genetics of the two mouse-adapted MERS strains allowed us to identify specific mutations that remained fixed through an additional 20 cycles of adaptive evolution. Our data indicate that the extent of MERS-CoV adaptation determines the minimal infectious dose required to achieve severe respiratory disease.</p>
</div>
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</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Virology</journal-id>
<journal-id journal-id-type="iso-abbrev">Virology</journal-id>
<journal-title-group><journal-title>Virology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0042-6822</issn>
<issn pub-type="epub">1096-0341</issn>
<publisher><publisher-name>Elsevier Inc.</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">29277291</article-id>
<article-id pub-id-type="pmc">5869108</article-id>
<article-id pub-id-type="publisher-id">S0042-6822(17)30411-7</article-id>
<article-id pub-id-type="doi">10.1016/j.virol.2017.12.006</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Adaptive evolution influences the infectious dose of MERS-CoV necessary to achieve severe respiratory disease</article-title>
</title-group>
<contrib-group><contrib contrib-type="author" id="au0005"><name><surname>Douglas</surname>
<given-names>Madeline G.</given-names>
</name>
<xref rid="aff0005" ref-type="aff">a</xref>
</contrib>
<contrib contrib-type="author" id="au0010"><name><surname>Kocher</surname>
<given-names>Jacob F.</given-names>
</name>
<xref rid="aff0005" ref-type="aff">a</xref>
</contrib>
<contrib contrib-type="author" id="au0015"><name><surname>Scobey</surname>
<given-names>Trevor</given-names>
</name>
<xref rid="aff0005" ref-type="aff">a</xref>
</contrib>
<contrib contrib-type="author" id="au0020"><name><surname>Baric</surname>
<given-names>Ralph S.</given-names>
</name>
<xref rid="aff0005" ref-type="aff">a</xref>
<xref rid="aff0010" ref-type="aff">b</xref>
<xref rid="fn1" ref-type="fn">1</xref>
</contrib>
<contrib contrib-type="author" id="au0025"><name><surname>Cockrell</surname>
<given-names>Adam S.</given-names>
</name>
<xref rid="aff0005" ref-type="aff">a</xref>
<xref rid="cor1" ref-type="corresp">⁎</xref>
<xref rid="fn1" ref-type="fn">1</xref>
</contrib>
</contrib-group>
<aff id="aff0005"><label>a</label>
Department of Epidemiology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA</aff>
<aff id="aff0010"><label>b</label>
Department of Microbiology and Immunology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27599, USA</aff>
<author-notes><corresp id="cor1"><label>⁎</label>
Corresponding author.</corresp>
<fn id="fn1"><label>1</label>
<p id="ntp0015">Co-Senior authors.</p>
</fn>
</author-notes>
<pub-date pub-type="pmc-release"><day>23</day>
<month>12</month>
<year>2017</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"><month>4</month>
<year>2018</year>
</pub-date>
<pub-date pub-type="epub"><day>23</day>
<month>12</month>
<year>2017</year>
</pub-date>
<volume>517</volume>
<fpage>98</fpage>
<lpage>107</lpage>
<history><date date-type="received"><day>30</day>
<month>9</month>
<year>2017</year>
</date>
<date date-type="rev-recd"><day>6</day>
<month>12</month>
<year>2017</year>
</date>
<date date-type="accepted"><day>11</day>
<month>12</month>
<year>2017</year>
</date>
</history>
<permissions><copyright-statement>© 2017 Elsevier Inc.</copyright-statement>
<copyright-year>2017</copyright-year>
<copyright-holder>Elsevier Inc.</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 id="ab0010"><p>We recently established a mouse model (288–330<sup>+/+</sup>
) that developed acute respiratory disease resembling human pathology following infection with a high dose (5 × 10<sup>6</sup>
PFU) of mouse-adapted MERS-CoV (icMERSma1). Although this high dose conferred fatal respiratory disease in mice, achieving similar pathology at lower viral doses may more closely reflect naturally acquired infections. Through continued adaptive evolution of icMERSma1 we generated a novel mouse-adapted MERS-CoV (maM35c4) capable of achieving severe respiratory disease at doses between 10<sup>3</sup>
and 10<sup>5</sup>
PFU. Novel mutations were identified in the maM35c4 genome that may be responsible for eliciting etiologies of acute respiratory distress syndrome at 10–1000 fold lower viral doses. Importantly, comparative genetics of the two mouse-adapted MERS strains allowed us to identify specific mutations that remained fixed through an additional 20 cycles of adaptive evolution. Our data indicate that the extent of MERS-CoV adaptation determines the minimal infectious dose required to achieve severe respiratory disease.</p>
</abstract>
<abstract abstract-type="author-highlights" id="ab0015"><title>Highlights</title>
<p><list list-type="simple" id="li0005"><list-item id="u0005"><label>•</label>
<p id="p0005">Mouse-adapted MERS-CoV can elicit severe respiratory disease at doses ranging 10<sup>3</sup>
–10<sup>5</sup>
PFU.</p>
</list-item>
<list-item id="u0010"><label>•</label>
<p id="p0010">Novel mutations in MERS-CoV may be associated with severe respiratory disease.</p>
</list-item>
<list-item id="u0015"><label>•</label>
<p id="p0015">The extent of MERS-CoV adaptation determines the minimal effective dose to elicit respiratory disease.</p>
</list-item>
</list>
</p>
</abstract>
<kwd-group id="keys0005"><title>Keywords</title>
<kwd>Coronavirus</kwd>
<kwd>MERS-CoV</kwd>
<kwd>Middle East respiratory syndrome</kwd>
<kwd>Respiratory disease</kwd>
<kwd>Acute respiratory distress syndrome</kwd>
<kwd>Spike protein</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
</record>
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