Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection.
Identifieur interne : 000855 ( PubMed/Curation ); précédent : 000854; suivant : 000856Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection.
Auteurs : Vineet D. Menachery [États-Unis] ; Kenneth H. Dinnon [États-Unis] ; Boyd L. Yount [États-Unis] ; Eileen T. Mcanarney [États-Unis] ; Lisa E. Gralinski [États-Unis] ; Andrew Hale [États-Unis] ; Rachel L. Graham [États-Unis] ; Trevor Scobey [États-Unis] ; Simon J. Anthony [États-Unis] ; Lingshu Wang [États-Unis] ; Barney Graham [États-Unis] ; Scott H. Randell [États-Unis] ; W Ian Lipkin [États-Unis] ; Ralph S. Baric [États-Unis]Source :
- Journal of virology [ 1098-5514 ] ; 2020.
Abstract
Traditionally, the emergence of coronaviruses (CoVs) has been attributed to a gain in receptor binding in a new host. Our previous work with severe acute respiratory syndrome (SARS)-like viruses argued that bats already harbor CoVs with the ability to infect humans without adaptation. These results suggested that additional barriers limit the emergence of zoonotic CoV. In this work, we describe overcoming host restriction of two Middle East respiratory syndrome (MERS)-like bat CoVs using exogenous protease treatment. We found that the spike protein of PDF2180-CoV, a MERS-like virus found in a Ugandan bat, could mediate infection of Vero and human cells in the presence of exogenous trypsin. We subsequently show that the bat virus spike can mediate the infection of human gut cells but is unable to infect human lung cells. Using receptor-blocking antibodies, we show that infection with the PDF2180 spike does not require MERS-CoV receptor DPP4 and antibodies developed against the MERS spike receptor-binding domain and S2 portion are ineffective in neutralizing the PDF2180 chimera. Finally, we found that the addition of exogenous trypsin also rescues HKU5-CoV, a second bat group 2c CoV. Together, these results indicate that proteolytic cleavage of the spike, not receptor binding, is the primary infection barrier for these two group 2c CoVs. Coupled with receptor binding, proteolytic activation offers a new parameter to evaluate the emergence potential of bat CoVs and offers a means to recover previously unrecoverable zoonotic CoV strains.IMPORTANCE Overall, our studies demonstrate that proteolytic cleavage is the primary barrier to infection for a subset of zoonotic coronaviruses. Moving forward, the results argue that both receptor binding and proteolytic cleavage of the spike are critical factors that must be considered for evaluating the emergence potential and risk posed by zoonotic coronaviruses. In addition, the findings also offer a novel means to recover previously uncultivable zoonotic coronavirus strains and argue that other tissues, including the digestive tract, could be a site for future coronavirus emergence events in humans.
DOI: 10.1128/JVI.01774-19
PubMed: 31801868
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Menachery</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas</wicri:regionArea></affiliation></author><author><name sortKey="Dinnon, Kenneth H" sort="Dinnon, Kenneth H" uniqKey="Dinnon K" first="Kenneth H" last="Dinnon">Kenneth H. Dinnon</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Yount, Boyd L" sort="Yount, Boyd L" uniqKey="Yount B" first="Boyd L" last="Yount">Boyd L. Yount</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Mcanarney, Eileen T" sort="Mcanarney, Eileen T" uniqKey="Mcanarney E" first="Eileen T" last="Mcanarney">Eileen T. Mcanarney</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas</wicri:regionArea></affiliation></author><author><name sortKey="Gralinski, Lisa E" sort="Gralinski, Lisa E" uniqKey="Gralinski L" first="Lisa E" last="Gralinski">Lisa E. Gralinski</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Hale, Andrew" sort="Hale, Andrew" uniqKey="Hale A" first="Andrew" last="Hale">Andrew Hale</name><affiliation wicri:level="1"><nlm:affiliation>Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Graham, Rachel L" sort="Graham, Rachel L" uniqKey="Graham R" first="Rachel L" last="Graham">Rachel L. Graham</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Scobey, Trevor" sort="Scobey, Trevor" uniqKey="Scobey T" first="Trevor" last="Scobey">Trevor Scobey</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea></affiliation></author><author><name sortKey="Anthony, Simon J" sort="Anthony, Simon J" uniqKey="Anthony S" first="Simon J" last="Anthony">Simon J. Anthony</name><affiliation wicri:level="1"><nlm:affiliation>Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York</wicri:regionArea></affiliation></author><author><name sortKey="Wang, Lingshu" sort="Wang, Lingshu" uniqKey="Wang L" first="Lingshu" last="Wang">Lingshu Wang</name><affiliation wicri:level="1"><nlm:affiliation>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Graham, Barney" sort="Graham, Barney" uniqKey="Graham B" first="Barney" last="Graham">Barney Graham</name><affiliation wicri:level="1"><nlm:affiliation>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland</wicri:regionArea></affiliation></author><author><name sortKey="Randell, Scott H" sort="Randell, Scott H" uniqKey="Randell S" first="Scott H" last="Randell">Scott H. Randell</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cell Biology and Physiology, and Marsico Lung Institute/Cystic Fibrosis Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Caroline du Nord</region></placeName><wicri:cityArea>Department of Cell Biology and Physiology, and Marsico Lung Institute/Cystic Fibrosis Center, University of North Carolina at Chapel Hill, Chapel Hill</wicri:cityArea></affiliation></author><author><name sortKey="Lipkin, W Ian" sort="Lipkin, W Ian" uniqKey="Lipkin W" first="W Ian" last="Lipkin">W Ian Lipkin</name><affiliation wicri:level="1"><nlm:affiliation>Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York</wicri:regionArea></affiliation></author><author><name sortKey="Baric, Ralph S" sort="Baric, Ralph S" uniqKey="Baric R" first="Ralph S" last="Baric">Ralph S. Baric</name><affiliation wicri:level="1"><nlm:affiliation>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA Rbaric@email.unc.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina</wicri:regionArea></affiliation></author></analytic><series><title level="j">Journal of virology</title><idno type="eISSN">1098-5514</idno><imprint><date when="2020" type="published">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Traditionally, the emergence of coronaviruses (CoVs) has been attributed to a gain in receptor binding in a new host. Our previous work with severe acute respiratory syndrome (SARS)-like viruses argued that bats already harbor CoVs with the ability to infect humans without adaptation. These results suggested that additional barriers limit the emergence of zoonotic CoV. In this work, we describe overcoming host restriction of two Middle East respiratory syndrome (MERS)-like bat CoVs using exogenous protease treatment. We found that the spike protein of PDF2180-CoV, a MERS-like virus found in a Ugandan bat, could mediate infection of Vero and human cells in the presence of exogenous trypsin. We subsequently show that the bat virus spike can mediate the infection of human gut cells but is unable to infect human lung cells. Using receptor-blocking antibodies, we show that infection with the PDF2180 spike does not require MERS-CoV receptor DPP4 and antibodies developed against the MERS spike receptor-binding domain and S2 portion are ineffective in neutralizing the PDF2180 chimera. Finally, we found that the addition of exogenous trypsin also rescues HKU5-CoV, a second bat group 2c CoV. Together, these results indicate that proteolytic cleavage of the spike, not receptor binding, is the primary infection barrier for these two group 2c CoVs. Coupled with receptor binding, proteolytic activation offers a new parameter to evaluate the emergence potential of bat CoVs and offers a means to recover previously unrecoverable zoonotic CoV strains.<b>IMPORTANCE</b> Overall, our studies demonstrate that proteolytic cleavage is the primary barrier to infection for a subset of zoonotic coronaviruses. Moving forward, the results argue that both receptor binding and proteolytic cleavage of the spike are critical factors that must be considered for evaluating the emergence potential and risk posed by zoonotic coronaviruses. In addition, the findings also offer a novel means to recover previously uncultivable zoonotic coronavirus strains and argue that other tissues, including the digestive tract, could be a site for future coronavirus emergence events in humans.</div></front></TEI><pubmed><MedlineCitation Status="In-Data-Review" Owner="NLM"><PMID Version="1">31801868</PMID><DateRevised><Year>2020</Year><Month>04</Month><Day>20</Day></DateRevised><Article PubModel="Electronic-Print"><Journal><ISSN IssnType="Electronic">1098-5514</ISSN><JournalIssue CitedMedium="Internet"><Volume>94</Volume><Issue>5</Issue><PubDate><Year>2020</Year><Month>Feb</Month><Day>14</Day></PubDate></JournalIssue><Title>Journal of virology</Title><ISOAbbreviation>J. Virol.</ISOAbbreviation></Journal><ArticleTitle>Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection.</ArticleTitle><ELocationID EIdType="pii" ValidYN="Y">e01774-19</ELocationID><ELocationID EIdType="doi" ValidYN="Y">10.1128/JVI.01774-19</ELocationID><Abstract><AbstractText>Traditionally, the emergence of coronaviruses (CoVs) has been attributed to a gain in receptor binding in a new host. Our previous work with severe acute respiratory syndrome (SARS)-like viruses argued that bats already harbor CoVs with the ability to infect humans without adaptation. These results suggested that additional barriers limit the emergence of zoonotic CoV. In this work, we describe overcoming host restriction of two Middle East respiratory syndrome (MERS)-like bat CoVs using exogenous protease treatment. We found that the spike protein of PDF2180-CoV, a MERS-like virus found in a Ugandan bat, could mediate infection of Vero and human cells in the presence of exogenous trypsin. We subsequently show that the bat virus spike can mediate the infection of human gut cells but is unable to infect human lung cells. Using receptor-blocking antibodies, we show that infection with the PDF2180 spike does not require MERS-CoV receptor DPP4 and antibodies developed against the MERS spike receptor-binding domain and S2 portion are ineffective in neutralizing the PDF2180 chimera. Finally, we found that the addition of exogenous trypsin also rescues HKU5-CoV, a second bat group 2c CoV. Together, these results indicate that proteolytic cleavage of the spike, not receptor binding, is the primary infection barrier for these two group 2c CoVs. Coupled with receptor binding, proteolytic activation offers a new parameter to evaluate the emergence potential of bat CoVs and offers a means to recover previously unrecoverable zoonotic CoV strains.<b>IMPORTANCE</b> Overall, our studies demonstrate that proteolytic cleavage is the primary barrier to infection for a subset of zoonotic coronaviruses. Moving forward, the results argue that both receptor binding and proteolytic cleavage of the spike are critical factors that must be considered for evaluating the emergence potential and risk posed by zoonotic coronaviruses. In addition, the findings also offer a novel means to recover previously uncultivable zoonotic coronavirus strains and argue that other tissues, including the digestive tract, could be a site for future coronavirus emergence events in humans.</AbstractText><CopyrightInformation>Copyright © 2020 American Society for Microbiology.</CopyrightInformation></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Menachery</LastName><ForeName>Vineet D</ForeName><Initials>VD</Initials><Identifier Source="ORCID">https://orcid.org/0000-0001-8803-7606</Identifier><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dinnon</LastName><ForeName>Kenneth H</ForeName><Initials>KH</Initials><Suffix>3rd</Suffix><AffiliationInfo><Affiliation>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yount</LastName><ForeName>Boyd L</ForeName><Initials>BL</Initials><Suffix>Jr</Suffix><AffiliationInfo><Affiliation>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McAnarney</LastName><ForeName>Eileen T</ForeName><Initials>ET</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gralinski</LastName><ForeName>Lisa E</ForeName><Initials>LE</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hale</LastName><ForeName>Andrew</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Graham</LastName><ForeName>Rachel L</ForeName><Initials>RL</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Scobey</LastName><ForeName>Trevor</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Anthony</LastName><ForeName>Simon J</ForeName><Initials>SJ</Initials><AffiliationInfo><Affiliation>Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Lingshu</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Graham</LastName><ForeName>Barney</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Vaccine Research Center, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Randell</LastName><ForeName>Scott H</ForeName><Initials>SH</Initials><AffiliationInfo><Affiliation>Department of Cell Biology and Physiology, and Marsico Lung Institute/Cystic Fibrosis Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lipkin</LastName><ForeName>W Ian</ForeName><Initials>WI</Initials><AffiliationInfo><Affiliation>Center for Infection and Immunity, Mailman School of Public Health, Columbia University, New York, New York, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Baric</LastName><ForeName>Ralph S</ForeName><Initials>RS</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA Rbaric@email.unc.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, 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28;503(7477):535-8</Citation><ArticleIdList><ArticleId IdType="pubmed">24172901</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>mBio. 2014 Mar 25;5(2):e00047-14</Citation><ArticleIdList><ArticleId IdType="pubmed">24667706</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Virology. 1975 Dec;68(2):426-39</Citation><ArticleIdList><ArticleId IdType="pubmed">173078</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Sci Adv. 2017 Nov 15;3(11):eaao4966</Citation><ArticleIdList><ArticleId IdType="pubmed">29152574</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Proteome Res. 2011 Dec 2;10(12):5363-73</Citation><ArticleIdList><ArticleId IdType="pubmed">21967108</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2013 Apr;87(7):3885-902</Citation><ArticleIdList><ArticleId IdType="pubmed">23365422</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Virus Res. 2008 Apr;133(1):33-44</Citation><ArticleIdList><ArticleId IdType="pubmed">17451829</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2009 Jul;83(14):7062-74</Citation><ArticleIdList><ArticleId IdType="pubmed">19420084</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 2017 Aug 29;114(35):E7348-E7357</Citation><ArticleIdList><ArticleId IdType="pubmed">28807998</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2008 Sep;82(17):8721-32</Citation><ArticleIdList><ArticleId IdType="pubmed">18579604</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Virology. 1992 Nov;191(1):517-22</Citation><ArticleIdList><ArticleId IdType="pubmed">1413526</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 1987 Dec;61(12):3749-53</Citation><ArticleIdList><ArticleId IdType="pubmed">2824812</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>mBio. 2013 Sep 10;4(5):e00650-13</Citation><ArticleIdList><ArticleId IdType="pubmed">24023385</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 2015 Aug 18;112(33):10473-8</Citation><ArticleIdList><ArticleId IdType="pubmed">26216974</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Viruses. 2018 Feb 24;10(2):</Citation><ArticleIdList><ArticleId IdType="pubmed">29495250</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Sci Transl Med. 2017 Jun 28;9(396):</Citation><ArticleIdList><ArticleId IdType="pubmed">28659436</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 1981 Sep;39(3):816-22</Citation><ArticleIdList><ArticleId IdType="pubmed">6169841</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2012 Dec;86(23):12816-25</Citation><ArticleIdList><ArticleId IdType="pubmed">22993147</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Virus Genes. 2012 Apr;44(2):167-75</Citation><ArticleIdList><ArticleId IdType="pubmed">22270324</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nature. 2018 Apr;556(7700):255-258</Citation><ArticleIdList><ArticleId IdType="pubmed">29618817</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>N Engl J Med. 2012 Nov 8;367(19):1814-20</Citation><ArticleIdList><ArticleId IdType="pubmed">23075143</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):E8508-E8517</Citation><ArticleIdList><ArticleId IdType="pubmed">28923942</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Infect Dis. 2014 Apr 1;209(7):995-1006</Citation><ArticleIdList><ArticleId IdType="pubmed">24253287</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Philos Trans R Soc Lond B Biol Sci. 2017 Jul 19;372(1725):</Citation><ArticleIdList><ArticleId IdType="pubmed">28584175</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2011 Dec;85(23):12201-15</Citation><ArticleIdList><ArticleId IdType="pubmed">21937658</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol Methods. 2009 Mar;156(1-2):19-26</Citation><ArticleIdList><ArticleId IdType="pubmed">19027037</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2014 Jul;88(14):7952-61</Citation><ArticleIdList><ArticleId IdType="pubmed">24807723</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Virus Res. 2015 Apr 16;202:120-34</Citation><ArticleIdList><ArticleId IdType="pubmed">25445340</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 2014 Aug 26;111(34):12516-21</Citation><ArticleIdList><ArticleId IdType="pubmed">25114257</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Pathol. 2004 Jun;203(2):622-30</Citation><ArticleIdList><ArticleId IdType="pubmed">15141376</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Gen Virol. 2013 Aug;94(Pt 8):1749-1760</Citation><ArticleIdList><ArticleId IdType="pubmed">23620378</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19944-9</Citation><ArticleIdList><ArticleId IdType="pubmed">19036930</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Virology. 2018 Apr;517:30-37</Citation><ArticleIdList><ArticleId IdType="pubmed">29279138</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Clin Microbiol. 2015 May;53(5):1537-48</Citation><ArticleIdList><ArticleId IdType="pubmed">25740769</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>mBio. 2017 Apr 4;8(2):</Citation><ArticleIdList><ArticleId IdType="pubmed">28377531</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Vaccine. 2017 Aug 16;35(35 Pt A):4470-4474</Citation><ArticleIdList><ArticleId IdType="pubmed">28633891</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2018 Nov 27;92(24):</Citation><ArticleIdList><ArticleId IdType="pubmed">30258004</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Virology. 2007 Feb 20;358(2):424-35</Citation><ArticleIdList><ArticleId IdType="pubmed">17023013</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 2017 Apr 11;114(15):E3119-E3128</Citation><ArticleIdList><ArticleId IdType="pubmed">28348219</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3048-53</Citation><ArticleIdList><ArticleId IdType="pubmed">26976607</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Rev Med Virol. 2015 Nov;25(6):406-30</Citation><ArticleIdList><ArticleId IdType="pubmed">26467906</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):16157-62</Citation><ArticleIdList><ArticleId IdType="pubmed">24043791</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Lancet. 2012 Dec 1;380(9857):1956-65</Citation><ArticleIdList><ArticleId IdType="pubmed">23200504</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>PLoS Pathog. 2017 Jul 31;13(7):e1006546</Citation><ArticleIdList><ArticleId IdType="pubmed">28759649</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2011 Jan;85(1):217-30</Citation><ArticleIdList><ArticleId IdType="pubmed">20980507</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nat Rev Microbiol. 2009 Jun;7(6):439-50</Citation><ArticleIdList><ArticleId IdType="pubmed">19430490</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Clin Microbiol. 1988 Nov;26(11):2235-9</Citation><ArticleIdList><ArticleId IdType="pubmed">2853174</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Adv Virus Res. 2016;96:193-218</Citation><ArticleIdList><ArticleId IdType="pubmed">27712624</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Sci Rep. 2018 Nov 9;8(1):16597</Citation><ArticleIdList><ArticleId IdType="pubmed">30413791</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2016 Jun 24;90(14):6573-6582</Citation><ArticleIdList><ArticleId IdType="pubmed">27170748</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 2005 Aug 30;102(35):12543-7</Citation><ArticleIdList><ArticleId IdType="pubmed">16116101</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Nat Med. 2015 Dec;21(12):1508-13</Citation><ArticleIdList><ArticleId IdType="pubmed">26552008</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>Proc Natl Acad Sci U S A. 2016 Oct 25;113(43):12262-12267</Citation><ArticleIdList><ArticleId IdType="pubmed">27791014</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2018 Jun 13;92(13):</Citation><ArticleIdList><ArticleId IdType="pubmed">29669833</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2008 Mar;82(5):2274-85</Citation><ArticleIdList><ArticleId IdType="pubmed">18094188</ArticleId></ArticleIdList></Reference></ReferenceList><ReferenceList><Reference><Citation>J Virol. 2018 May 14;92(11):</Citation><ArticleIdList><ArticleId 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