Adaptive Gene Amplification As an Intermediate Step in the Expansion of Virus Host Range
Identifieur interne : 001408 ( Pmc/Curation ); précédent : 001407; suivant : 001409Adaptive Gene Amplification As an Intermediate Step in the Expansion of Virus Host Range
Auteurs : Greg Brennan [États-Unis] ; Jacob O. Kitzman [États-Unis] ; Stefan Rothenburg [États-Unis] ; Jay Shendure [États-Unis] ; Adam P. Geballe [États-Unis]Source :
- PLoS Pathogens [ 1553-7366 ] ; 2014.
Abstract
The majority of recently emerging infectious diseases in humans is due to cross-species pathogen transmissions from animals. To establish a productive infection in new host species, viruses must overcome barriers to replication mediated by diverse and rapidly evolving host restriction factors such as protein kinase R (PKR). Many viral antagonists of these restriction factors are species specific. For example, the rhesus cytomegalovirus PKR antagonist, RhTRS1, inhibits PKR in some African green monkey (AGM) cells, but does not inhibit human or rhesus macaque PKR. To model the evolutionary changes necessary for cross-species transmission, we generated a recombinant vaccinia virus that expresses RhTRS1 in a strain that lacks PKR inhibitors E3L and K3L (VVΔEΔK+RhTRS1). Serially passaging VVΔEΔK+RhTRS1 in minimally-permissive AGM cells increased viral replication 10- to 100-fold. Notably, adaptation in these AGM cells also improved virus replication 1000- to 10,000-fold in human and rhesus cells. Genetic analyses including deep sequencing revealed amplification of the
Url:
DOI: 10.1371/journal.ppat.1004002
PubMed: 24626510
PubMed Central: 3953438
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Kitzman</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genome Sciences, University of Washington, Seattle, Washington</wicri:regionArea></affiliation></author><author><name sortKey="Rothenburg, Stefan" sort="Rothenburg, Stefan" uniqKey="Rothenburg S" first="Stefan" last="Rothenburg">Stefan Rothenburg</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Division of Biology, Kansas State University, Manhattan, Kansas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Biology, Kansas State University, Manhattan, Kansas</wicri:regionArea></affiliation></author><author><name sortKey="Shendure, Jay" sort="Shendure, Jay" uniqKey="Shendure J" first="Jay" last="Shendure">Jay Shendure</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genome Sciences, University of Washington, Seattle, Washington</wicri:regionArea></affiliation></author><author><name sortKey="Geballe, Adam P" sort="Geballe, Adam P" uniqKey="Geballe A" first="Adam P." last="Geballe">Adam P. Geballe</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Departments of Microbiology and Medicine, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Departments of Microbiology and Medicine, University of Washington, Seattle, Washington</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24626510</idno><idno type="pmc">3953438</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3953438</idno><idno type="RBID">PMC:3953438</idno><idno type="doi">10.1371/journal.ppat.1004002</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">001408</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001408</idno><idno type="wicri:Area/Pmc/Curation">001408</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">001408</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Adaptive Gene Amplification As an Intermediate Step in the Expansion of Virus Host Range</title><author><name sortKey="Brennan, Greg" sort="Brennan, Greg" uniqKey="Brennan G" first="Greg" last="Brennan">Greg Brennan</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea></affiliation></author><author><name sortKey="Kitzman, Jacob O" sort="Kitzman, Jacob O" uniqKey="Kitzman J" first="Jacob O." last="Kitzman">Jacob O. Kitzman</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genome Sciences, University of Washington, Seattle, Washington</wicri:regionArea></affiliation></author><author><name sortKey="Rothenburg, Stefan" sort="Rothenburg, Stefan" uniqKey="Rothenburg S" first="Stefan" last="Rothenburg">Stefan Rothenburg</name><affiliation wicri:level="1"><nlm:aff id="aff3"><addr-line>Division of Biology, Kansas State University, Manhattan, Kansas, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Biology, Kansas State University, Manhattan, Kansas</wicri:regionArea></affiliation></author><author><name sortKey="Shendure, Jay" sort="Shendure, Jay" uniqKey="Shendure J" first="Jay" last="Shendure">Jay Shendure</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Genome Sciences, University of Washington, Seattle, Washington</wicri:regionArea></affiliation></author><author><name sortKey="Geballe, Adam P" sort="Geballe, Adam P" uniqKey="Geballe A" first="Adam P." last="Geballe">Adam P. Geballe</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><addr-line>Departments of Microbiology and Medicine, University of Washington, Seattle, Washington, United States of America</addr-line></nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Departments of Microbiology and Medicine, University of Washington, Seattle, Washington</wicri:regionArea></affiliation></author></analytic><series><title level="j">PLoS Pathogens</title><idno type="ISSN">1553-7366</idno><idno type="eISSN">1553-7374</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>The majority of recently emerging infectious diseases in humans is due to cross-species pathogen transmissions from animals. To establish a productive infection in new host species, viruses must overcome barriers to replication mediated by diverse and rapidly evolving host restriction factors such as protein kinase R (PKR). Many viral antagonists of these restriction factors are species specific. For example, the rhesus cytomegalovirus PKR antagonist, RhTRS1, inhibits PKR in some African green monkey (AGM) cells, but does not inhibit human or rhesus macaque PKR. To model the evolutionary changes necessary for cross-species transmission, we generated a recombinant vaccinia virus that expresses RhTRS1 in a strain that lacks PKR inhibitors E3L and K3L (VVΔEΔK+RhTRS1). Serially passaging VVΔEΔK+RhTRS1 in minimally-permissive AGM cells increased viral replication 10- to 100-fold. Notably, adaptation in these AGM cells also improved virus replication 1000- to 10,000-fold in human and rhesus cells. Genetic analyses including deep sequencing revealed amplification of the <italic>rhtrs1</italic> locus in the adapted viruses. Supplying additional <italic>rhtrs1</italic> in <italic>trans</italic> confirmed that amplification alone was sufficient to improve VVΔEΔK+RhTRS1 replication. Viruses with amplified <italic>rhtrs1</italic> completely blocked AGM PKR, but only partially blocked human PKR, consistent with the replication properties of these viruses in AGM and human cells. Finally, in contrast to AGM-adapted viruses, which could be serially propagated in human cells, VVΔEΔK+RhTRS1 yielded no progeny virus after only three passages in human cells. Thus, <italic>rhtrs1</italic> amplification in a minimally permissive intermediate host was a necessary step, enabling expansion of the virus range to previously nonpermissive hosts. These data support the hypothesis that amplification of a weak viral antagonist may be a general evolutionary mechanism to permit replication in otherwise resistant host species, providing a molecular foothold that could enable further adaptations necessary for efficient replication in the new host.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Yamada, A" uniqKey="Yamada A">A Yamada</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mahy, Bw" uniqKey="Mahy B">BW Mahy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bengis, Rg" uniqKey="Bengis R">RG Bengis</name></author><author><name sortKey="Leighton, Fa" uniqKey="Leighton F">FA Leighton</name></author><author><name sortKey="Fischer, Jr" uniqKey="Fischer J">JR Fischer</name></author><author><name sortKey="Artois, M" uniqKey="Artois M">M Artois</name></author><author><name sortKey="Morner, T" uniqKey="Morner T">T Morner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Parrish, Cr" uniqKey="Parrish C">CR Parrish</name></author><author><name sortKey="Holmes, Ec" uniqKey="Holmes E">EC Holmes</name></author><author><name sortKey="Morens, Dm" uniqKey="Morens D">DM Morens</name></author><author><name sortKey="Park, Ec" uniqKey="Park E">EC Park</name></author><author><name sortKey="Burke, Ds" uniqKey="Burke D">DS Burke</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chua, Kb" uniqKey="Chua K">KB Chua</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Sharp, Pm" uniqKey="Sharp P">PM Sharp</name></author><author><name sortKey="Hahn, Bh" uniqKey="Hahn B">BH Hahn</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stremlau, M" uniqKey="Stremlau M">M Stremlau</name></author><author><name sortKey="Owens, Cm" uniqKey="Owens C">CM Owens</name></author><author><name sortKey="Perron, Mj" uniqKey="Perron M">MJ Perron</name></author><author><name sortKey="Kiessling, M" uniqKey="Kiessling M">M Kiessling</name></author><author><name sortKey="Autissier, P" uniqKey="Autissier P">P Autissier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sadler, Aj" uniqKey="Sadler A">AJ Sadler</name></author><author><name sortKey="Williams, Br" uniqKey="Williams B">BR Williams</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Daugherty, Md" uniqKey="Daugherty M">MD Daugherty</name></author><author><name sortKey="Malik, Hs" uniqKey="Malik H">HS Malik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Elde, Nc" uniqKey="Elde N">NC Elde</name></author><author><name sortKey="Child, Sj" uniqKey="Child S">SJ Child</name></author><author><name sortKey="Geballe, Ap" uniqKey="Geballe A">AP Geballe</name></author><author><name sortKey="Malik, Hs" uniqKey="Malik H">HS Malik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rothenburg, S" uniqKey="Rothenburg S">S Rothenburg</name></author><author><name sortKey="Seo, Ej" uniqKey="Seo E">EJ Seo</name></author><author><name sortKey="Gibbs, Js" uniqKey="Gibbs J">JS Gibbs</name></author><author><name sortKey="Dever, Te" uniqKey="Dever T">TE Dever</name></author><author><name sortKey="Dittmar, K" uniqKey="Dittmar K">K Dittmar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Brown, Cj" uniqKey="Brown C">CJ Brown</name></author><author><name sortKey="Todd, Km" uniqKey="Todd K">KM Todd</name></author><author><name sortKey="Rosenzweig, Rf" uniqKey="Rosenzweig R">RF Rosenzweig</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gonzalez, E" uniqKey="Gonzalez E">E Gonzalez</name></author><author><name sortKey="Kulkarni, H" uniqKey="Kulkarni H">H Kulkarni</name></author><author><name sortKey="Bolivar, H" uniqKey="Bolivar H">H Bolivar</name></author><author><name sortKey="Mangano, A" uniqKey="Mangano A">A Mangano</name></author><author><name sortKey="Sanchez, R" uniqKey="Sanchez R">R Sanchez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Roth, Jr" uniqKey="Roth J">JR Roth</name></author><author><name sortKey="Andersson, Di" uniqKey="Andersson D">DI Andersson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Elde, Nc" uniqKey="Elde N">NC Elde</name></author><author><name sortKey="Child, Sj" uniqKey="Child S">SJ Child</name></author><author><name sortKey="Eickbush, Mt" uniqKey="Eickbush M">MT Eickbush</name></author><author><name sortKey="Kitzman, Jo" uniqKey="Kitzman J">JO Kitzman</name></author><author><name sortKey="Rogers, Ks" uniqKey="Rogers K">KS Rogers</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Slabaugh, M" uniqKey="Slabaugh M">M Slabaugh</name></author><author><name sortKey="Roseman, N" uniqKey="Roseman N">N Roseman</name></author><author><name sortKey="Davis, R" uniqKey="Davis R">R Davis</name></author><author><name sortKey="Mathews, C" uniqKey="Mathews C">C Mathews</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kondrashov, Fa" uniqKey="Kondrashov F">FA Kondrashov</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Child, Sj" uniqKey="Child S">SJ Child</name></author><author><name sortKey="Brennan, G" uniqKey="Brennan G">G Brennan</name></author><author><name sortKey="Braggin, Je" uniqKey="Braggin J">JE Braggin</name></author><author><name sortKey="Geballe, Ap" uniqKey="Geballe A">AP Geballe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Slabaugh, Mb" uniqKey="Slabaugh M">MB Slabaugh</name></author><author><name sortKey="Roseman, Na" uniqKey="Roseman N">NA Roseman</name></author><author><name sortKey="Mathews, Ck" uniqKey="Mathews C">CK Mathews</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Child, Sj" uniqKey="Child S">SJ Child</name></author><author><name sortKey="Brennan, G" uniqKey="Brennan G">G Brennan</name></author><author><name sortKey="Braggin, Je" uniqKey="Braggin J">JE Braggin</name></author><author><name sortKey="Geballe, Ap" uniqKey="Geballe A">AP Geballe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Garcia, Ma" uniqKey="Garcia M">MA Garcia</name></author><author><name sortKey="Meurs, Ef" uniqKey="Meurs E">EF Meurs</name></author><author><name sortKey="Esteban, M" uniqKey="Esteban M">M Esteban</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jones, Ke" uniqKey="Jones K">KE Jones</name></author><author><name sortKey="Patel, Ng" uniqKey="Patel N">NG Patel</name></author><author><name sortKey="Levy, Ma" uniqKey="Levy M">MA Levy</name></author><author><name sortKey="Storeygard, A" uniqKey="Storeygard A">A Storeygard</name></author><author><name sortKey="Balk, D" uniqKey="Balk D">D Balk</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bayliss, Cd" uniqKey="Bayliss C">CD Bayliss</name></author><author><name sortKey="Condit, Rc" uniqKey="Condit R">RC Condit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cresawn, Sg" uniqKey="Cresawn S">SG Cresawn</name></author><author><name sortKey="Prins, C" uniqKey="Prins C">C Prins</name></author><author><name sortKey="Latner, Dr" uniqKey="Latner D">DR Latner</name></author><author><name sortKey="Condit, Rc" uniqKey="Condit R">RC Condit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rehm, Ke" uniqKey="Rehm K">KE Rehm</name></author><author><name sortKey="Connor, Rf" uniqKey="Connor R">RF Connor</name></author><author><name sortKey="Jones, Gj" uniqKey="Jones G">GJ Jones</name></author><author><name sortKey="Yimbu, K" uniqKey="Yimbu K">K Yimbu</name></author><author><name sortKey="Roper, Rl" uniqKey="Roper R">RL Roper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rehm, Ke" uniqKey="Rehm K">KE Rehm</name></author><author><name sortKey="Roper, Rl" uniqKey="Roper R">RL Roper</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Talloczy, Z" uniqKey="Talloczy Z">Z Talloczy</name></author><author><name sortKey="Jiang, W" uniqKey="Jiang W">W Jiang</name></author><author><name sortKey="Virgin, Hw" uniqKey="Virgin H">HW Virgin</name></author><author><name sortKey="Leib, Da" uniqKey="Leib D">DA Leib</name></author><author><name sortKey="Scheuner, D" uniqKey="Scheuner D">D Scheuner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lu, B" uniqKey="Lu B">B Lu</name></author><author><name sortKey="Nakamura, T" uniqKey="Nakamura T">T Nakamura</name></author><author><name sortKey="Inouye, K" uniqKey="Inouye K">K Inouye</name></author><author><name sortKey="Li, J" uniqKey="Li J">J Li</name></author><author><name sortKey="Tang, Y" uniqKey="Tang Y">Y Tang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hett, Ec" uniqKey="Hett E">EC Hett</name></author><author><name sortKey="Slater, Lh" uniqKey="Slater L">LH Slater</name></author><author><name sortKey="Mark, Kg" uniqKey="Mark K">KG Mark</name></author><author><name sortKey="Kawate, T" uniqKey="Kawate T">T Kawate</name></author><author><name sortKey="Monks, Bg" uniqKey="Monks B">BG Monks</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Child, Sj" uniqKey="Child S">SJ Child</name></author><author><name sortKey="Hakki, M" uniqKey="Hakki M">M Hakki</name></author><author><name sortKey="De Niro, Kl" uniqKey="De Niro K">KL De Niro</name></author><author><name sortKey="Geballe, Ap" uniqKey="Geballe A">AP Geballe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tartaglia, J" uniqKey="Tartaglia J">J Tartaglia</name></author><author><name sortKey="Perkus, Me" uniqKey="Perkus M">ME Perkus</name></author><author><name sortKey="Taylor, J" uniqKey="Taylor J">J Taylor</name></author><author><name sortKey="Norton, Ek" uniqKey="Norton E">EK Norton</name></author><author><name sortKey="Audonnet, Jc" uniqKey="Audonnet J">JC Audonnet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beattie, E" uniqKey="Beattie E">E Beattie</name></author><author><name sortKey="Paoletti, E" uniqKey="Paoletti E">E Paoletti</name></author><author><name sortKey="Tartaglia, J" uniqKey="Tartaglia J">J Tartaglia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beattie, E" uniqKey="Beattie E">E Beattie</name></author><author><name sortKey="Tartaglia, J" uniqKey="Tartaglia J">J Tartaglia</name></author><author><name sortKey="Paoletti, E" uniqKey="Paoletti E">E Paoletti</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rahman, Mm" uniqKey="Rahman M">MM Rahman</name></author><author><name sortKey="Liu, J" uniqKey="Liu J">J Liu</name></author><author><name sortKey="Chan, Wm" uniqKey="Chan W">WM Chan</name></author><author><name sortKey="Rothenburg, S" uniqKey="Rothenburg S">S Rothenburg</name></author><author><name sortKey="Mcfadden, G" uniqKey="Mcfadden G">G McFadden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Marshall, Ee" uniqKey="Marshall E">EE Marshall</name></author><author><name sortKey="Bierle, Cj" uniqKey="Bierle C">CJ Bierle</name></author><author><name sortKey="Brune, W" uniqKey="Brune W">W Brune</name></author><author><name sortKey="Geballe, Ap" uniqKey="Geballe A">AP Geballe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chenna, R" uniqKey="Chenna R">R Chenna</name></author><author><name sortKey="Sugawara, H" uniqKey="Sugawara H">H Sugawara</name></author><author><name sortKey="Koike, T" uniqKey="Koike T">T Koike</name></author><author><name sortKey="Lopez, R" uniqKey="Lopez R">R Lopez</name></author><author><name sortKey="Gibson, Tj" uniqKey="Gibson T">TJ Gibson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Esposito, J" uniqKey="Esposito J">J Esposito</name></author><author><name sortKey="Condit, R" uniqKey="Condit R">R Condit</name></author><author><name sortKey="Obijeski, J" uniqKey="Obijeski J">J Obijeski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Simpson, Jt" uniqKey="Simpson J">JT Simpson</name></author><author><name sortKey="Wong, K" uniqKey="Wong K">K Wong</name></author><author><name sortKey="Jackman, Sd" uniqKey="Jackman S">SD Jackman</name></author><author><name sortKey="Schein, Je" uniqKey="Schein J">JE Schein</name></author><author><name sortKey="Jones, Sj" uniqKey="Jones S">SJ Jones</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, H" uniqKey="Li H">H Li</name></author><author><name sortKey="Durbin, R" uniqKey="Durbin R">R Durbin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mckenna, A" uniqKey="Mckenna A">A McKenna</name></author><author><name sortKey="Hanna, M" uniqKey="Hanna M">M Hanna</name></author><author><name sortKey="Banks, E" uniqKey="Banks E">E Banks</name></author><author><name sortKey="Sivachenko, A" uniqKey="Sivachenko A">A Sivachenko</name></author><author><name sortKey="Cibulskis, K" uniqKey="Cibulskis K">K Cibulskis</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Li, H" uniqKey="Li H">H Li</name></author><author><name sortKey="Durbin, R" uniqKey="Durbin R">R Durbin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kurtz, S" uniqKey="Kurtz S">S Kurtz</name></author><author><name sortKey="Phillippy, A" uniqKey="Phillippy A">A Phillippy</name></author><author><name sortKey="Delcher, Al" uniqKey="Delcher A">AL Delcher</name></author><author><name sortKey="Smoot, M" uniqKey="Smoot M">M Smoot</name></author><author><name sortKey="Shumway, M" uniqKey="Shumway M">M Shumway</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS Pathog</journal-id><journal-id journal-id-type="iso-abbrev">PLoS Pathog</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plospath</journal-id><journal-title-group><journal-title>PLoS Pathogens</journal-title></journal-title-group><issn pub-type="ppub">1553-7366</issn><issn pub-type="epub">1553-7374</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24626510</article-id><article-id pub-id-type="pmc">3953438</article-id><article-id pub-id-type="publisher-id">PPATHOGENS-D-13-02391</article-id><article-id pub-id-type="doi">10.1371/journal.ppat.1004002</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology</subject><subj-group><subject>Evolutionary Biology</subject></subj-group><subj-group><subject>Microbiology</subject><subj-group><subject>Virology</subject><subj-group><subject>Mechanisms of Resistance and Susceptibility</subject><subject>Viral Evolution</subject><subject>Viral Immune Evasion</subject></subj-group></subj-group><subj-group><subject>Host-Pathogen Interaction</subject><subject>Microbial Evolution</subject></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine</subject><subj-group><subject>Infectious Diseases</subject><subj-group><subject>Viral Diseases</subject></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Adaptive Gene Amplification As an Intermediate Step in the Expansion of Virus Host Range</article-title><alt-title alt-title-type="running-head">Gene Amplification Expands Viral Host Range</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Brennan</surname><given-names>Greg</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kitzman</surname><given-names>Jacob O.</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rothenburg</surname><given-names>Stefan</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Shendure</surname><given-names>Jay</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Geballe</surname><given-names>Adam P.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><xref ref-type="aff" rid="aff5"><sup>5</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Department of Genome Sciences, University of Washington, Seattle, Washington, United States of America</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Division of Biology, Kansas State University, Manhattan, Kansas, United States of America</addr-line></aff><aff id="aff4"><label>4</label><addr-line>Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America</addr-line></aff><aff id="aff5"><label>5</label><addr-line>Departments of Microbiology and Medicine, University of Washington, Seattle, Washington, United States of America</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Condit</surname><given-names>Richard C.</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>University of Florida, United States of America</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>ageballe@fhcrc.org</email></corresp><fn fn-type="COI-statement"><p>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con"><p>Conceived and designed the experiments: GB JOK SR JS APG. Performed the experiments: GB JOK APG. Analyzed the data: GB JOK JS APG. Wrote the paper: GB JOK SR JS APG.</p></fn></author-notes><pub-date pub-type="collection"><month>3</month><year>2014</year></pub-date><pub-date pub-type="epub"><day>13</day><month>3</month><year>2014</year></pub-date><volume>10</volume><issue>3</issue><elocation-id>e1004002</elocation-id><history><date date-type="received"><day>12</day><month>9</month><year>2013</year></date><date date-type="accepted"><day>1</day><month>2</month><year>2014</year></date></history><permissions><copyright-statement>© 2014 Brennan et al</copyright-statement><copyright-year>2014</copyright-year><copyright-holder>Brennan et al</copyright-holder><license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p></license></permissions><abstract><p>The majority of recently emerging infectious diseases in humans is due to cross-species pathogen transmissions from animals. To establish a productive infection in new host species, viruses must overcome barriers to replication mediated by diverse and rapidly evolving host restriction factors such as protein kinase R (PKR). Many viral antagonists of these restriction factors are species specific. For example, the rhesus cytomegalovirus PKR antagonist, RhTRS1, inhibits PKR in some African green monkey (AGM) cells, but does not inhibit human or rhesus macaque PKR. To model the evolutionary changes necessary for cross-species transmission, we generated a recombinant vaccinia virus that expresses RhTRS1 in a strain that lacks PKR inhibitors E3L and K3L (VVΔEΔK+RhTRS1). Serially passaging VVΔEΔK+RhTRS1 in minimally-permissive AGM cells increased viral replication 10- to 100-fold. Notably, adaptation in these AGM cells also improved virus replication 1000- to 10,000-fold in human and rhesus cells. Genetic analyses including deep sequencing revealed amplification of the <italic>rhtrs1</italic> locus in the adapted viruses. Supplying additional <italic>rhtrs1</italic> in <italic>trans</italic> confirmed that amplification alone was sufficient to improve VVΔEΔK+RhTRS1 replication. Viruses with amplified <italic>rhtrs1</italic> completely blocked AGM PKR, but only partially blocked human PKR, consistent with the replication properties of these viruses in AGM and human cells. Finally, in contrast to AGM-adapted viruses, which could be serially propagated in human cells, VVΔEΔK+RhTRS1 yielded no progeny virus after only three passages in human cells. Thus, <italic>rhtrs1</italic> amplification in a minimally permissive intermediate host was a necessary step, enabling expansion of the virus range to previously nonpermissive hosts. These data support the hypothesis that amplification of a weak viral antagonist may be a general evolutionary mechanism to permit replication in otherwise resistant host species, providing a molecular foothold that could enable further adaptations necessary for efficient replication in the new host.</p></abstract><abstract abstract-type="summary"><title>Author Summary</title><p>The spread of microbes from animals to humans has been responsible for most recently emerging human infectious diseases, including AIDS, bird flu, and SARS. Therefore, understanding the evolutionary and molecular mechanisms underlying cross-species transmission is of critical importance for public health. After entering a new host cell, the success of a virus depends on its ability to overcome antiviral factors in the cell, such as protein kinase R (PKR). To investigate the process of virus transmission between species, we employed a recombinant vaccinia virus (VVΔEΔK+RhTRS1) expressing the rhesus cytomegalovirus PKR antagonist RhTRS1. This protein inhibits some African green monkey (AGM) PKRs; however, it does not inhibit human or rhesus variants of PKR. Serial passaging VVΔEΔK+RhTRS1 in RhTRS1-resistant AGM cells resulted in <italic>rhtrs1</italic> duplication in the viral genome, which improved VVΔEΔK+RhTRS1 replication in AGM cells. Remarkably, <italic>rhtrs1</italic> duplication also enhanced virus replication in human and rhesus cells. In contrast, passage of VVΔEΔK+RhTRS1 in human cells, without prior adaptation in AGM cells, did not improve VVΔEΔK+RhTRS1 replication. These results support the hypothesis that amplification of a weak viral antagonist of a host defense protein in one species may enable cross-species transmission into new hosts that are nonpermissive to the initial virus.</p></abstract><funding-group><funding-statement>This work was supported by NIH (<ext-link ext-link-type="uri" xlink:href="http://www.nih.gov">http://www.nih.gov</ext-link>) AI027762 (to APG), NIH 1R21CA160080-01 (to JS), a National Science Foundation (<ext-link ext-link-type="uri" xlink:href="http://www.nsf.gov">http://www.nsf.gov</ext-link>) Graduate Research Fellowship (to JOK), NIH P20 RR016475 (to SR), and an American Cancer Society (<ext-link ext-link-type="uri" xlink:href="http://www.cancer.org">http://www.cancer.org</ext-link>) Postdoctoral Fellowship (to GB). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><page-count count="12"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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