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<title xml:lang="en">Pandemic Swine H1N1 Influenza Viruses with Almost Undetectable Neuraminidase Activity Are Not Transmitted via Aerosols in Ferrets and Are Inhibited by Human Mucus but Not Swine Mucus</title>
<author>
<name sortKey="Zanin, Mark" sort="Zanin, Mark" uniqKey="Zanin M" first="Mark" last="Zanin">Mark Zanin</name>
<affiliation>
<nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Marathe, Bindumadhav" sort="Marathe, Bindumadhav" uniqKey="Marathe B" first="Bindumadhav" last="Marathe">Bindumadhav Marathe</name>
<affiliation>
<nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Wong, Sook San" sort="Wong, Sook San" uniqKey="Wong S" first="Sook-San" last="Wong">Sook-San Wong</name>
<affiliation>
<nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Yoon, Sun Woo" sort="Yoon, Sun Woo" uniqKey="Yoon S" first="Sun-Woo" last="Yoon">Sun-Woo Yoon</name>
<affiliation>
<nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Collin, Emily" sort="Collin, Emily" uniqKey="Collin E" first="Emily" last="Collin">Emily Collin</name>
<affiliation>
<nlm:aff id="aff2">Newport Laboratories, Worthington, Minnesota, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Oshansky, Christine" sort="Oshansky, Christine" uniqKey="Oshansky C" first="Christine" last="Oshansky">Christine Oshansky</name>
<affiliation>
<nlm:aff id="aff3">Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Jones, Jeremy" sort="Jones, Jeremy" uniqKey="Jones J" first="Jeremy" last="Jones">Jeremy Jones</name>
<affiliation>
<nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Hause, Benjamin" sort="Hause, Benjamin" uniqKey="Hause B" first="Benjamin" last="Hause">Benjamin Hause</name>
<affiliation>
<nlm:aff id="aff4">Veterinary Diagnostic Laboratory, Kansas State University, Manhattan, Kansas, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Webby, Richard" sort="Webby, Richard" uniqKey="Webby R" first="Richard" last="Webby">Richard Webby</name>
<affiliation>
<nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
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<idno type="pmid">25810540</idno>
<idno type="pmc">4442420</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4442420</idno>
<idno type="RBID">PMC:4442420</idno>
<idno type="doi">10.1128/JVI.02537-14</idno>
<date when="2015">2015</date>
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<title xml:lang="en" level="a" type="main">Pandemic Swine H1N1 Influenza Viruses with Almost Undetectable Neuraminidase Activity Are Not Transmitted via Aerosols in Ferrets and Are Inhibited by Human Mucus but Not Swine Mucus</title>
<author>
<name sortKey="Zanin, Mark" sort="Zanin, Mark" uniqKey="Zanin M" first="Mark" last="Zanin">Mark Zanin</name>
<affiliation>
<nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Marathe, Bindumadhav" sort="Marathe, Bindumadhav" uniqKey="Marathe B" first="Bindumadhav" last="Marathe">Bindumadhav Marathe</name>
<affiliation>
<nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Wong, Sook San" sort="Wong, Sook San" uniqKey="Wong S" first="Sook-San" last="Wong">Sook-San Wong</name>
<affiliation>
<nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Yoon, Sun Woo" sort="Yoon, Sun Woo" uniqKey="Yoon S" first="Sun-Woo" last="Yoon">Sun-Woo Yoon</name>
<affiliation>
<nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Collin, Emily" sort="Collin, Emily" uniqKey="Collin E" first="Emily" last="Collin">Emily Collin</name>
<affiliation>
<nlm:aff id="aff2">Newport Laboratories, Worthington, Minnesota, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Oshansky, Christine" sort="Oshansky, Christine" uniqKey="Oshansky C" first="Christine" last="Oshansky">Christine Oshansky</name>
<affiliation>
<nlm:aff id="aff3">Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Jones, Jeremy" sort="Jones, Jeremy" uniqKey="Jones J" first="Jeremy" last="Jones">Jeremy Jones</name>
<affiliation>
<nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Hause, Benjamin" sort="Hause, Benjamin" uniqKey="Hause B" first="Benjamin" last="Hause">Benjamin Hause</name>
<affiliation>
<nlm:aff id="aff4">Veterinary Diagnostic Laboratory, Kansas State University, Manhattan, Kansas, USA</nlm:aff>
</affiliation>
</author>
<author>
<name sortKey="Webby, Richard" sort="Webby, Richard" uniqKey="Webby R" first="Richard" last="Webby">Richard Webby</name>
<affiliation>
<nlm:aff id="aff1">Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</nlm:aff>
</affiliation>
</author>
</analytic>
<series>
<title level="j">Journal of Virology</title>
<idno type="ISSN">0022-538X</idno>
<idno type="eISSN">1098-5514</idno>
<imprint>
<date when="2015">2015</date>
</imprint>
</series>
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<front>
<div type="abstract" xml:lang="en">
<title>ABSTRACT</title>
<p>A balance between the functions of the influenza virus surface proteins hemagglutinin (HA) and neuraminidase (NA) is thought to be important for the transmission of viruses between humans. Here we describe two pandemic H1N1 viruses, A/swine/Virginia/1814-1/2012 and A/swine/Virginia/1814-2/2012 (pH1N1
<sub>low</sub>
-1 and -2, respectively), that were isolated from swine symptomatic for influenza. The enzymatic activity of the NA of these viruses was almost undetectable, while the HA binding affinity for α2,6 sialic acids was greater than that of the highly homologous pH1N1 viruses A/swine/Pennsylvania/2436/2012 and A/swine/Minnesota/2499/2012 (pH1N1-1 and -2), which exhibited better-balanced HA and NA activities. The
<italic>in vitro</italic>
growth kinetics of pH1N1
<sub>low</sub>
and pH1N1 viruses were similar, but aerosol transmission of pH1N1
<sub>low</sub>
-1 was abrogated and transmission via direct contact in ferrets was significantly impaired compared to pH1N1-1, which transmitted by direct and aerosol contact. In normal human bronchial epithelial cells, pH1N1
<sub>low</sub>
-1 was significantly inhibited by mucus but pH1N1-1 was not. In Madin-Darby canine kidney cell cultures overlaid with human or swine mucus, human mucus inhibited pH1N1
<sub>low</sub>
-1 but swine mucus did not. These data show that the interaction between viruses and mucus may be an important factor in viral transmissibility and could be a barrier for interspecies transmission between humans and swine for influenza viruses.</p>
<p>
<bold>IMPORTANCE</bold>
A balance between the functions of the influenza virus surface proteins hemagglutinin (HA) and neuraminidase (NA) is thought to be important for transmission of viruses from swine to humans. Here we show that a swine virus with extremely functionally mismatched HA and NAs (pH1N1
<sub>low</sub>
-1) cannot transmit via aerosol in ferrets, while another highly homologous virus with HA and NAs that are better matched functionally (pH1N1-1) can transmit via aerosol. These viruses show similar growth kinetics in Madin-Darby canine kidney (MDCK) cells, but pH1N1
<sub>low</sub>
-1 is significantly inhibited by mucus in normal human bronchial epithelial cells whereas pH1N1-1 is not. Further, human mucus could inhibit these viruses, but swine mucus could not. These data show that the interaction between viruses and mucus may be an important factor in viral transmissibility and could be a species barrier between humans and swine for influenza viruses.</p>
</div>
</front>
</TEI>
<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>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">J Virol</journal-id>
<journal-id journal-id-type="iso-abbrev">J. Virol</journal-id>
<journal-id journal-id-type="hwp">jvi</journal-id>
<journal-id journal-id-type="pmc">jvi</journal-id>
<journal-id journal-id-type="publisher-id">JVI</journal-id>
<journal-title-group>
<journal-title>Journal of Virology</journal-title>
</journal-title-group>
<issn pub-type="ppub">0022-538X</issn>
<issn pub-type="epub">1098-5514</issn>
<publisher>
<publisher-name>American Society for Microbiology</publisher-name>
<publisher-loc>1752 N St., N.W., Washington, DC</publisher-loc>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">25810540</article-id>
<article-id pub-id-type="pmc">4442420</article-id>
<article-id pub-id-type="publisher-id">02537-14</article-id>
<article-id pub-id-type="doi">10.1128/JVI.02537-14</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Pathogenesis and Immunity</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Pandemic Swine H1N1 Influenza Viruses with Almost Undetectable Neuraminidase Activity Are Not Transmitted via Aerosols in Ferrets and Are Inhibited by Human Mucus but Not Swine Mucus</article-title>
<alt-title alt-title-type="running-head">Low Neuraminidase-Activity H1N1 Virus Transmissibility</alt-title>
<alt-title alt-title-type="short-authors">Zanin et al.</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Zanin</surname>
<given-names>Mark</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Marathe</surname>
<given-names>Bindumadhav</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wong</surname>
<given-names>Sook-San</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Yoon</surname>
<given-names>Sun-Woo</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
<xref ref-type="author-notes" rid="fn1">*</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Collin</surname>
<given-names>Emily</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Oshansky</surname>
<given-names>Christine</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>c</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Jones</surname>
<given-names>Jeremy</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Hause</surname>
<given-names>Benjamin</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>d</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Webby</surname>
<given-names>Richard</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
</contrib>
<aff id="aff1">
<label>a</label>
Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</aff>
<aff id="aff2">
<label>b</label>
Newport Laboratories, Worthington, Minnesota, USA</aff>
<aff id="aff3">
<label>c</label>
Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA</aff>
<aff id="aff4">
<label>d</label>
Veterinary Diagnostic Laboratory, Kansas State University, Manhattan, Kansas, USA</aff>
</contrib-group>
<contrib-group>
<contrib contrib-type="editor">
<name>
<surname>Perlman</surname>
<given-names>S.</given-names>
</name>
<role>Editor</role>
</contrib>
</contrib-group>
<author-notes>
<corresp id="cor1">Address correspondence to Richard Webby,
<email>richard.webby@stjude.org</email>
.</corresp>
<fn id="fn1" fn-type="present-address">
<label>*</label>
<p>Present address: Sun-Woo Yoon, Viral Infectious Disease Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, South Korea.</p>
</fn>
<fn fn-type="other">
<p>
<bold>Citation</bold>
Zanin M, Marathe B, Wong S-S, Yoon S-W, Collin E, Oshansky C, Jones J, Hause B, Webby R. 2015. Pandemic swine H1N1 influenza viruses with almost undetectable neuraminidase activity are not transmitted via aerosols in ferrets and are inhibited by human mucus but not swine mucus. J Virol 89:5935–5948. doi:
<ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.1128/JVI.02537-14">10.1128/JVI.02537-14</ext-link>
.</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>25</day>
<month>3</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="collection">
<day>1</day>
<month>6</month>
<year>2015</year>
</pub-date>
<volume>89</volume>
<issue>11</issue>
<fpage>5935</fpage>
<lpage>5948</lpage>
<history>
<date date-type="received">
<day>5</day>
<month>9</month>
<year>2014</year>
</date>
<date date-type="accepted">
<day>12</day>
<month>3</month>
<year>2015</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2015, American Society for Microbiology. All Rights Reserved.</copyright-statement>
<copyright-year>2015</copyright-year>
<copyright-holder>American Society for Microbiology</copyright-holder>
</permissions>
<self-uri content-type="pdf" xlink:href="zjv01115005935.pdf"></self-uri>
<abstract>
<title>ABSTRACT</title>
<p>A balance between the functions of the influenza virus surface proteins hemagglutinin (HA) and neuraminidase (NA) is thought to be important for the transmission of viruses between humans. Here we describe two pandemic H1N1 viruses, A/swine/Virginia/1814-1/2012 and A/swine/Virginia/1814-2/2012 (pH1N1
<sub>low</sub>
-1 and -2, respectively), that were isolated from swine symptomatic for influenza. The enzymatic activity of the NA of these viruses was almost undetectable, while the HA binding affinity for α2,6 sialic acids was greater than that of the highly homologous pH1N1 viruses A/swine/Pennsylvania/2436/2012 and A/swine/Minnesota/2499/2012 (pH1N1-1 and -2), which exhibited better-balanced HA and NA activities. The
<italic>in vitro</italic>
growth kinetics of pH1N1
<sub>low</sub>
and pH1N1 viruses were similar, but aerosol transmission of pH1N1
<sub>low</sub>
-1 was abrogated and transmission via direct contact in ferrets was significantly impaired compared to pH1N1-1, which transmitted by direct and aerosol contact. In normal human bronchial epithelial cells, pH1N1
<sub>low</sub>
-1 was significantly inhibited by mucus but pH1N1-1 was not. In Madin-Darby canine kidney cell cultures overlaid with human or swine mucus, human mucus inhibited pH1N1
<sub>low</sub>
-1 but swine mucus did not. These data show that the interaction between viruses and mucus may be an important factor in viral transmissibility and could be a barrier for interspecies transmission between humans and swine for influenza viruses.</p>
<p>
<bold>IMPORTANCE</bold>
A balance between the functions of the influenza virus surface proteins hemagglutinin (HA) and neuraminidase (NA) is thought to be important for transmission of viruses from swine to humans. Here we show that a swine virus with extremely functionally mismatched HA and NAs (pH1N1
<sub>low</sub>
-1) cannot transmit via aerosol in ferrets, while another highly homologous virus with HA and NAs that are better matched functionally (pH1N1-1) can transmit via aerosol. These viruses show similar growth kinetics in Madin-Darby canine kidney (MDCK) cells, but pH1N1
<sub>low</sub>
-1 is significantly inhibited by mucus in normal human bronchial epithelial cells whereas pH1N1-1 is not. Further, human mucus could inhibit these viruses, but swine mucus could not. These data show that the interaction between viruses and mucus may be an important factor in viral transmissibility and could be a species barrier between humans and swine for influenza viruses.</p>
</abstract>
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</article-meta>
</front>
</pmc>
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