Influenza A Virus (H5N1) Infection in Cats Causes Systemic Disease with Potential Novel Routes of Virus Spread within and between Hosts
Identifieur interne : 000151 ( Pmc/Curation ); précédent : 000150; suivant : 000152Influenza A Virus (H5N1) Infection in Cats Causes Systemic Disease with Potential Novel Routes of Virus Spread within and between Hosts
Auteurs : Guus F. Rimmelzwaan ; Debby Van Riel ; Marianne Baars ; Theo M. Bestebroer ; Geert Van Amerongen ; Ron A. M. Fouchier ; Albert D. M. E. Osterhaus ; Thijs KuikenSource :
- The American Journal of Pathology [ 0002-9440 ] ; 2006.
Abstract
The ongoing outbreak of avian influenza A virus (subtype H5N1) infection in Asia is of great concern because of the high human case fatality rate and the threat of a new influenza pandemic. Case reports in humans and felids suggest that this virus may have a different tissue tropism from other influenza viruses, which are normally restricted to the respiratory tract in mammals. To study its pathogenesis in a mammalian host, domestic cats were inoculated with H5N1 virus intratracheally (
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PubMed: 16400021
PubMed Central: 1592682
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Influenza A Virus (H5N1) Infection in Cats Causes Systemic Disease with Potential Novel Routes of Virus Spread within and between Hosts</title>
<author><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name>
</author>
<author><name sortKey="Van Riel, Debby" sort="Van Riel, Debby" uniqKey="Van Riel D" first="Debby" last="Van Riel">Debby Van Riel</name>
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<author><name sortKey="Baars, Marianne" sort="Baars, Marianne" uniqKey="Baars M" first="Marianne" last="Baars">Marianne Baars</name>
</author>
<author><name sortKey="Bestebroer, Theo M" sort="Bestebroer, Theo M" uniqKey="Bestebroer T" first="Theo M." last="Bestebroer">Theo M. Bestebroer</name>
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<author><name sortKey="Van Amerongen, Geert" sort="Van Amerongen, Geert" uniqKey="Van Amerongen G" first="Geert" last="Van Amerongen">Geert Van Amerongen</name>
</author>
<author><name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A. M." last="Fouchier">Ron A. M. Fouchier</name>
</author>
<author><name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D. M. E." last="Osterhaus">Albert D. M. E. Osterhaus</name>
</author>
<author><name sortKey="Kuiken, Thijs" sort="Kuiken, Thijs" uniqKey="Kuiken T" first="Thijs" last="Kuiken">Thijs Kuiken</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Influenza A Virus (H5N1) Infection in Cats Causes Systemic Disease with Potential Novel Routes of Virus Spread within and between Hosts</title>
<author><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F." last="Rimmelzwaan">Guus F. Rimmelzwaan</name>
</author>
<author><name sortKey="Van Riel, Debby" sort="Van Riel, Debby" uniqKey="Van Riel D" first="Debby" last="Van Riel">Debby Van Riel</name>
</author>
<author><name sortKey="Baars, Marianne" sort="Baars, Marianne" uniqKey="Baars M" first="Marianne" last="Baars">Marianne Baars</name>
</author>
<author><name sortKey="Bestebroer, Theo M" sort="Bestebroer, Theo M" uniqKey="Bestebroer T" first="Theo M." last="Bestebroer">Theo M. Bestebroer</name>
</author>
<author><name sortKey="Van Amerongen, Geert" sort="Van Amerongen, Geert" uniqKey="Van Amerongen G" first="Geert" last="Van Amerongen">Geert Van Amerongen</name>
</author>
<author><name sortKey="Fouchier, Ron A M" sort="Fouchier, Ron A M" uniqKey="Fouchier R" first="Ron A. M." last="Fouchier">Ron A. M. Fouchier</name>
</author>
<author><name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D. M. E." last="Osterhaus">Albert D. M. E. Osterhaus</name>
</author>
<author><name sortKey="Kuiken, Thijs" sort="Kuiken, Thijs" uniqKey="Kuiken T" first="Thijs" last="Kuiken">Thijs Kuiken</name>
</author>
</analytic>
<series><title level="j">The American Journal of Pathology</title>
<idno type="ISSN">0002-9440</idno>
<idno type="eISSN">1525-2191</idno>
<imprint><date when="2006">2006</date>
</imprint>
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<front><div type="abstract" xml:lang="en"><p>The ongoing outbreak of avian influenza A virus (subtype H5N1) infection in Asia is of great concern because of the high human case fatality rate and the threat of a new influenza pandemic. Case reports in humans and felids suggest that this virus may have a different tissue tropism from other influenza viruses, which are normally restricted to the respiratory tract in mammals. To study its pathogenesis in a mammalian host, domestic cats were inoculated with H5N1 virus intratracheally (<bold><italic>n</italic>
</bold>
= 3), by feeding on virus-infected chicks (<bold><italic>n</italic>
</bold>
= 3), or by horizontal transmission (<bold><italic>n</italic>
</bold>
= 2) and examined by virological and pathological assays. In all cats, virus replicated not only in the respiratory tract but also in multiple extra-respiratory tissues. Virus antigen expression in these tissues was associated with severe necrosis and inflammation 7 days after inoculation. In cats fed on virus-infected chicks only, virus-associated ganglioneuritis also occurred in the submucosal and myenteric plexi of the small intestine, suggesting direct infection from the intestinal lumen. All cats excreted virus not only via the respiratory tract but also via the digestive tract. This study in cats demonstrates that H5N1 virus infection causes systemic disease and spreads by potentially novel routes within and between mammalian hosts.</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">Am J Pathol</journal-id>
<journal-title>The American Journal of Pathology</journal-title>
<issn pub-type="ppub">0002-9440</issn>
<issn pub-type="epub">1525-2191</issn>
<publisher><publisher-name>American Society for Investigative Pathology</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">16400021</article-id>
<article-id pub-id-type="pmc">1592682</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
<subj-group><subject>Immunopathology and Infectious Diseases</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group><article-title>Influenza A Virus (H5N1) Infection in Cats Causes Systemic Disease with Potential Novel Routes of Virus Spread within and between Hosts</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Rimmelzwaan</surname>
<given-names>Guus F.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>van Riel</surname>
<given-names>Debby</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Baars</surname>
<given-names>Marianne</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Bestebroer</surname>
<given-names>Theo M.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>van Amerongen</surname>
<given-names>Geert</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Fouchier</surname>
<given-names>Ron A.M.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Osterhaus</surname>
<given-names>Albert D.M.E.</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Kuiken</surname>
<given-names>Thijs</given-names>
</name>
</contrib>
<aff id="N0x2dd6a50N0x3d8e080">From the Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands</aff>
</contrib-group>
<pub-date pub-type="ppub"><month>1</month>
<year>2006</year>
</pub-date>
<volume>168</volume>
<issue>1</issue>
<fpage>176</fpage>
<lpage>183</lpage>
<history><date date-type="accepted"><day>3</day>
<month>10</month>
<year>2005</year>
</date>
</history>
<permissions><copyright-statement>Copyright © American Society for Investigative Pathology</copyright-statement>
<copyright-year>2006</copyright-year>
</permissions>
<abstract><p>The ongoing outbreak of avian influenza A virus (subtype H5N1) infection in Asia is of great concern because of the high human case fatality rate and the threat of a new influenza pandemic. Case reports in humans and felids suggest that this virus may have a different tissue tropism from other influenza viruses, which are normally restricted to the respiratory tract in mammals. To study its pathogenesis in a mammalian host, domestic cats were inoculated with H5N1 virus intratracheally (<bold><italic>n</italic>
</bold>
= 3), by feeding on virus-infected chicks (<bold><italic>n</italic>
</bold>
= 3), or by horizontal transmission (<bold><italic>n</italic>
</bold>
= 2) and examined by virological and pathological assays. In all cats, virus replicated not only in the respiratory tract but also in multiple extra-respiratory tissues. Virus antigen expression in these tissues was associated with severe necrosis and inflammation 7 days after inoculation. In cats fed on virus-infected chicks only, virus-associated ganglioneuritis also occurred in the submucosal and myenteric plexi of the small intestine, suggesting direct infection from the intestinal lumen. All cats excreted virus not only via the respiratory tract but also via the digestive tract. This study in cats demonstrates that H5N1 virus infection causes systemic disease and spreads by potentially novel routes within and between mammalian hosts.</p>
</abstract>
</article-meta>
</front>
<floats-wrap><fig position="float" id="F1-6703"><label>Figure 1-6703</label>
<caption><p>Infectious virus titers in pharyngeal, nasal, and rectal swabs obtained from cats infected with influenza A virus (H5N1) by the intratracheal route (<bold>top</bold>
, <bold>filled symbols</bold>
), by horizontal transmission (<bold>top</bold>
, <bold>open symbols</bold>
), or by feeding on virus-infected chicks (<bold>bottom</bold>
, <bold>filled symbols</bold>
) at various time points after infection. No virus was isolated from any swabs of negative control cats (data not shown).</p>
</caption>
<graphic xlink:href="zjh0010667030001"></graphic>
</fig>
<fig position="float" id="F2-6703"><label>Figure 2-6703</label>
<caption><p>Infectious virus titers in organ tissue homogenates obtained from cats infected with influenza A virus (H5N1) by the intratracheal route (cats 1 to 3), by horizontal transmission (cats 4 and 5), or by feeding on virus-infected chicks (cats 6 to 8) 7 days after infection. Organs that were tested included stomach (<bold>A</bold>
), liver (<bold>B</bold>
), kidney (<bold>C</bold>
), heart (<bold>D</bold>
), cerebrum (<bold>E</bold>
), cerebellum (<bold>F</bold>
), brain stem (<bold>G</bold>
), olfactory bulb (<bold>H</bold>
), nasal concha (<bold>I</bold>
), lung (<bold>J</bold>
), trachea (<bold>K</bold>
), jejunum (<bold>L</bold>
), tonsil (<bold>M</bold>
), eyelid (<bold>N</bold>
), tracheo-broncheal lymph node (<bold>O</bold>
), mesenteric lymph node (<bold>P</bold>
), and spleen (<bold>Q</bold>
).</p>
</caption>
<graphic xlink:href="zjh0010667030002"></graphic>
</fig>
<fig position="float" id="F3-6703"><label>Figure 3-6703</label>
<caption><p>Cats infected with influenza A virus (H5N1) (cats 1 to 8) have lesions associated with virus replication in multiple tissues. Necrotizing and inflammatory changes are seen in multiple tissues, except the spleen, of cats infected with H5N1 virus (<bold>first column</bold>
). See the text for a more detailed description of these lesions. The <bold>asterisk</bold>
indicates protein exudate in the Bowman’s capsule of a renal glomerulus. The two <bold>arrowheads</bold>
point to the inflamed myenteric plexus in the intestinal wall. Serial sections of these tissues (<bold>second column</bold>
) show that these lesions are closely associated with the expression of influenza virus antigen. Tissues of negative control cats (cats 9 and 10) show neither lesions (<bold>third column</bold>
) nor influenza virus antigen expression (<bold>fourth column</bold>
). Tissues were stained either with H&E or by immunohistochemistry using a monoclonal antibody against the nucleoprotein of influenza A virus as a primary antibody.</p>
</caption>
<graphic xlink:href="zjh0010667030003"></graphic>
</fig>
<table-wrap position="float" id="T1-6703"><label>Table 1-6703</label>
<caption><p>Influenza Virus Antigen Expression in Tissues of Cats Infected with Influenza A Virus (H5N1) by Different Inoculation Routes</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="2" align="center" valign="bottom">Tissue<xref rid="TFN1-1-6703" ref-type="other">*</xref>
</th>
<th colspan="3" rowspan="1" align="center" valign="bottom">Number of animals positive per method of inoculation
<hr></hr>
</th>
</tr>
<tr><th colspan="1" rowspan="1" align="center" valign="bottom">Intratracheal (<italic>n</italic>
= 3)</th>
<th colspan="1" rowspan="1" align="center" valign="bottom">Sentinel (<italic>n</italic>
= 2)</th>
<th colspan="1" rowspan="1" align="center" valign="bottom">Fed on virus-infected chicks (<italic>n</italic>
= 3)</th>
</tr>
</thead>
<tbody><tr><td>Liver</td>
<td>3</td>
<td>2</td>
<td>1</td>
</tr>
<tr><td>Kidney</td>
<td>1</td>
<td>0</td>
<td>1</td>
</tr>
<tr><td>Heart</td>
<td>3</td>
<td>0</td>
<td>2</td>
</tr>
<tr><td>Cerebrum</td>
<td>3</td>
<td>n.d.<xref rid="TFN1-2-6703" ref-type="other"><sup>†</sup>
</xref>
</td>
<td>3</td>
</tr>
<tr><td>Cerebellum</td>
<td>2</td>
<td>n.d.</td>
<td>1</td>
</tr>
<tr><td>Brain stem</td>
<td>3</td>
<td>n.d.</td>
<td>3</td>
</tr>
<tr><td>Olfactory bulb</td>
<td>3</td>
<td>n.d.</td>
<td>2</td>
</tr>
<tr><td>Lung</td>
<td>3</td>
<td>2</td>
<td>3</td>
</tr>
<tr><td>Duodenum</td>
<td>0</td>
<td>n.d.</td>
<td>2</td>
</tr>
<tr><td>Ileum</td>
<td>0</td>
<td>n.d.</td>
<td>1</td>
</tr>
<tr><td>Mesenteric lymph node</td>
<td>1</td>
<td>0</td>
<td>0</td>
</tr>
<tr><td>Spleen</td>
<td>2</td>
<td>2</td>
<td>0</td>
</tr>
<tr><td>Thymus</td>
<td>1</td>
<td>n.d.</td>
<td>0</td>
</tr>
<tr><td>Adrenal gland</td>
<td>3</td>
<td>1</td>
<td>3</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="TFN1-1-6703"><label>†</label>
<p>No virus antigen expression was seen in the following tissues of the above animals: tongue, nasal concha, nasal septum, trachea, eyelid, third eyelid, thyroid, salivary gland, tonsil, tracheo-bronchial lymph node, retropharyngeal lymph node, mandibular lymph node, bone marrow, esophagus, stomach, pancreas, jejunum, cecum, colon, and urinary bladder. </p>
</fn>
<fn id="TFN1-2-6703"><label>†</label>
<p>Not done. </p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-wrap>
</pmc>
</record>
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