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<title xml:lang="en">Host resistance influences patterns of experimental viral adaptation and virulence evolution</title>
<author>
<name sortKey="Kubinak, Jason L" sort="Kubinak, Jason L" uniqKey="Kubinak J" first="Jason L" last="Kubinak">Jason L. Kubinak</name>
<affiliation>
<nlm:aff id="A1">Division of Microbiology and Immunology; Department of Pathology; School of Medicine; University of Utah; Salt Lake City, UT USA</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A2">Department of Biology; University of Utah; Salt Lake City, UT USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Potts, Wayne K" sort="Potts, Wayne K" uniqKey="Potts W" first="Wayne K" last="Potts">Wayne K. Potts</name>
<affiliation>
<nlm:aff id="A2">Department of Biology; University of Utah; Salt Lake City, UT USA</nlm:aff>
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<idno type="pmid">23645287</idno>
<idno type="pmc">3714133</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3714133</idno>
<idno type="RBID">PMC:3714133</idno>
<idno type="doi">10.4161/viru.24724</idno>
<date when="2013">2013</date>
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<title xml:lang="en" level="a" type="main">Host resistance influences patterns of experimental viral adaptation and virulence evolution</title>
<author>
<name sortKey="Kubinak, Jason L" sort="Kubinak, Jason L" uniqKey="Kubinak J" first="Jason L" last="Kubinak">Jason L. Kubinak</name>
<affiliation>
<nlm:aff id="A1">Division of Microbiology and Immunology; Department of Pathology; School of Medicine; University of Utah; Salt Lake City, UT USA</nlm:aff>
</affiliation>
<affiliation>
<nlm:aff id="A2">Department of Biology; University of Utah; Salt Lake City, UT USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Potts, Wayne K" sort="Potts, Wayne K" uniqKey="Potts W" first="Wayne K" last="Potts">Wayne K. Potts</name>
<affiliation>
<nlm:aff id="A2">Department of Biology; University of Utah; Salt Lake City, UT USA</nlm:aff>
</affiliation>
</author>
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<series>
<title level="j">Virulence</title>
<idno type="ISSN">2150-5594</idno>
<idno type="eISSN">2150-5608</idno>
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<date when="2013">2013</date>
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<p>Infectious diseases are major threats to all living systems, so understanding the forces of selection that limit the evolution of more virulent pathogens is of fundamental importance; this includes the practical application of identifying possible mitigation strategies for at-risk host populations. The evolution of more virulent pathogens has been classically understood to be limited by the tradeoff between within-host growth rate and transmissibility. Importantly, heterogeneity among hosts can influence both of these factors. However, despite our substantial understanding of how the immune system operates to control pathogen replication during infection, we have only a limited appreciation of how variability in intrinsic (i.e., genetically determined) levels of host resistance influences patterns of pathogen adaptation and virulence evolution. Here, we describe results from experimental evolution studies using a model host–pathogen (virus–mammal) system; we demonstrate that variability in intrinsic levels of resistance among host genotypes can have significant effects on patterns of pathogen adaptation and virulence evolution during serial passage. Both the magnitude of adaptive response as well as the degree of pathogen specialization was positively correlated with host resistance, while mean overall virulence of post-passage virus was negatively correlated with host resistance. These results are consistent with a model whereby resistant host genotypes impose stronger selection on adapting pathogen populations, which in turn leads to the evolution of more specialized pathogen variants whose overall (i.e., mean) virulence across host genotypes is reduced.</p>
</div>
</front>
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<pmc article-type="research-article">
<pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
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<journal-meta>
<journal-id journal-id-type="nlm-ta">Virulence</journal-id>
<journal-id journal-id-type="iso-abbrev">Virulence</journal-id>
<journal-id journal-id-type="publisher-id">VIRU</journal-id>
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<journal-title>Virulence</journal-title>
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<issn pub-type="ppub">2150-5594</issn>
<issn pub-type="epub">2150-5608</issn>
<publisher>
<publisher-name>Landes Bioscience</publisher-name>
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<article-id pub-id-type="pmid">23645287</article-id>
<article-id pub-id-type="pmc">3714133</article-id>
<article-id pub-id-type="publisher-id">2012VIRULENCE0168R</article-id>
<article-id pub-id-type="pii">24724</article-id>
<article-id pub-id-type="doi">10.4161/viru.24724</article-id>
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<subj-group subj-group-type="heading">
<subject>Research Paper</subject>
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<title-group>
<article-title>Host resistance influences patterns of experimental viral adaptation and virulence evolution</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Kubinak</surname>
<given-names>Jason L</given-names>
</name>
<xref ref-type="aff" rid="A1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="A2">
<sup>2</sup>
</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
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<contrib contrib-type="author">
<name>
<surname>Potts</surname>
<given-names>Wayne K</given-names>
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<xref ref-type="aff" rid="A2">
<sup>2</sup>
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<aff id="A1">
<label>1</label>
Division of Microbiology and Immunology; Department of Pathology; School of Medicine; University of Utah; Salt Lake City, UT USA</aff>
<aff id="A2">
<label>2</label>
Department of Biology; University of Utah; Salt Lake City, UT USA</aff>
</contrib-group>
<author-notes>
<corresp id="cor1">
<label>*</label>
Correspondence to: Jason L Kubinak; Email:
<email xlink:href="drjlkub@gmail.com">drjlkub@gmail.com</email>
</corresp>
</author-notes>
<pub-date pub-type="ppub">
<day>01</day>
<month>7</month>
<year>2013</year>
</pub-date>
<pub-date pub-type="epub">
<day>17</day>
<month>4</month>
<year>2013</year>
</pub-date>
<volume>4</volume>
<issue>5</issue>
<fpage>410</fpage>
<lpage>418</lpage>
<history>
<date date-type="received">
<day>24</day>
<month>1</month>
<year>2013</year>
</date>
<date date-type="rev-recd">
<day>15</day>
<month>4</month>
<year>2013</year>
</date>
<date date-type="accepted">
<day>16</day>
<month>4</month>
<year>2013</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2013 Landes Bioscience</copyright-statement>
<copyright-year>2013</copyright-year>
</permissions>
<abstract>
<p>Infectious diseases are major threats to all living systems, so understanding the forces of selection that limit the evolution of more virulent pathogens is of fundamental importance; this includes the practical application of identifying possible mitigation strategies for at-risk host populations. The evolution of more virulent pathogens has been classically understood to be limited by the tradeoff between within-host growth rate and transmissibility. Importantly, heterogeneity among hosts can influence both of these factors. However, despite our substantial understanding of how the immune system operates to control pathogen replication during infection, we have only a limited appreciation of how variability in intrinsic (i.e., genetically determined) levels of host resistance influences patterns of pathogen adaptation and virulence evolution. Here, we describe results from experimental evolution studies using a model host–pathogen (virus–mammal) system; we demonstrate that variability in intrinsic levels of resistance among host genotypes can have significant effects on patterns of pathogen adaptation and virulence evolution during serial passage. Both the magnitude of adaptive response as well as the degree of pathogen specialization was positively correlated with host resistance, while mean overall virulence of post-passage virus was negatively correlated with host resistance. These results are consistent with a model whereby resistant host genotypes impose stronger selection on adapting pathogen populations, which in turn leads to the evolution of more specialized pathogen variants whose overall (i.e., mean) virulence across host genotypes is reduced.</p>
</abstract>
<kwd-group kwd-group-type="author">
<title>Keywords: </title>
<kwd>host resistance</kwd>
<kwd>genetic diversity</kwd>
<kwd>viral adaptation</kwd>
<kwd>serial passage</kwd>
<kwd>experimental evolution</kwd>
</kwd-group>
</article-meta>
</front>
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