Animal Models for Influenza Virus Pathogenesis and Transmission
Identifieur interne : 000631 ( Ncbi/Merge ); précédent : 000630; suivant : 000632Animal Models for Influenza Virus Pathogenesis and Transmission
Auteurs : Nicole M. Bouvier [États-Unis] ; Anice C. Lowen [États-Unis]Source :
- Viruses [ 1999-4915 ] ; 2010.
Abstract
Influenza virus infection of humans results in a respiratory disease that ranges in severity from sub-clinical infection to primary viral pneumonia that can result in death. The clinical effects of infection vary with the exposure history, age and immune status of the host, and also the virulence of the influenza strain. In humans, the virus is transmitted through either aerosol or contact-based transfer of infectious respiratory secretions. As is evidenced by most zoonotic influenza virus infections, not all strains that can infect humans are able to transmit from person-to-person. Animal models of influenza are essential to research efforts aimed at understanding the viral and host factors that contribute to the disease and transmission outcomes of influenza virus infection in humans. These models furthermore allow the pre-clinical testing of antiviral drugs and vaccines aimed at reducing morbidity and mortality in the population through amelioration of the virulence or transmissibility of influenza viruses. Mice, ferrets, guinea pigs, cotton rats, hamsters and macaques have all been used to study influenza viruses and therapeutics targeting them. Each model presents unique advantages and disadvantages, which will be discussed herein.
Url:
DOI: 10.3390/v20801530
PubMed: 21442033
PubMed Central: 3063653
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<front><div type="abstract" xml:lang="en"><p>Influenza virus infection of humans results in a respiratory disease that ranges in severity from sub-clinical infection to primary viral pneumonia that can result in death. The clinical effects of infection vary with the exposure history, age and immune status of the host, and also the virulence of the influenza strain. In humans, the virus is transmitted through either aerosol or contact-based transfer of infectious respiratory secretions. As is evidenced by most zoonotic influenza virus infections, not all strains that can infect humans are able to transmit from person-to-person. Animal models of influenza are essential to research efforts aimed at understanding the viral and host factors that contribute to the disease and transmission outcomes of influenza virus infection in humans. These models furthermore allow the pre-clinical testing of antiviral drugs and vaccines aimed at reducing morbidity and mortality in the population through amelioration of the virulence or transmissibility of influenza viruses. Mice, ferrets, guinea pigs, cotton rats, hamsters and macaques have all been used to study influenza viruses and therapeutics targeting them. Each model presents unique advantages and disadvantages, which will be discussed herein.</p>
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</TEI>
<pmc article-type="review-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Viruses</journal-id>
<journal-title-group><journal-title>Viruses</journal-title>
</journal-title-group>
<issn pub-type="epub">1999-4915</issn>
<publisher><publisher-name>Molecular Diversity Preservation International (MDPI)</publisher-name>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">21442033</article-id>
<article-id pub-id-type="pmc">3063653</article-id>
<article-id pub-id-type="doi">10.3390/v20801530</article-id>
<article-id pub-id-type="publisher-id">viruses-02-01530</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Review</subject>
</subj-group>
</article-categories>
<title-group><article-title>Animal Models for Influenza Virus Pathogenesis and Transmission</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Bouvier</surname>
<given-names>Nicole M.</given-names>
</name>
<xref ref-type="aff" rid="af1-viruses-02-01530"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="af2-viruses-02-01530"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Lowen</surname>
<given-names>Anice C.</given-names>
</name>
<xref ref-type="aff" rid="af2-viruses-02-01530"><sup>2</sup>
</xref>
<xref ref-type="corresp" rid="c1-viruses-02-01530"><sup>*</sup>
</xref>
</contrib>
</contrib-group>
<aff id="af1-viruses-02-01530"><label>1</label>
Division of Infectious Diseases, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA; E-Mail:<email>nicole.bouvier@mssm.edu</email>
</aff>
<aff id="af2-viruses-02-01530"><label>2</label>
Department of Microbiology, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA</aff>
<author-notes><corresp id="c1-viruses-02-01530"><label>*</label>
Author to whom correspondence should be addressed; E-Mail: <email>anice.lowen@mssm.edu</email>
; Tel.: +1-212-241-7094; Fax: +1-212-534-1684.</corresp>
</author-notes>
<pub-date pub-type="collection"><month>8</month>
<year>2010</year>
</pub-date>
<pub-date pub-type="epub"><day>27</day>
<month>7</month>
<year>2010</year>
</pub-date>
<volume>2</volume>
<issue>8</issue>
<fpage>1530</fpage>
<lpage>1563</lpage>
<history><date date-type="received"><day>18</day>
<month>3</month>
<year>2010</year>
</date>
<date date-type="rev-recd"><day>12</day>
<month>7</month>
<year>2010</year>
</date>
<date date-type="accepted"><day>22</day>
<month>7</month>
<year>2010</year>
</date>
</history>
<permissions><copyright-statement>© 2010 by the authors; licensee MDPI, Basel, Switzerland.</copyright-statement>
<copyright-year>2010</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/3.0"><license-p><pmc-comment>CREATIVE COMMONS</pmc-comment>
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/3.0/">http://creativecommons.org/licenses/by/3.0/</ext-link>
).</license-p>
</license>
</permissions>
<abstract><p>Influenza virus infection of humans results in a respiratory disease that ranges in severity from sub-clinical infection to primary viral pneumonia that can result in death. The clinical effects of infection vary with the exposure history, age and immune status of the host, and also the virulence of the influenza strain. In humans, the virus is transmitted through either aerosol or contact-based transfer of infectious respiratory secretions. As is evidenced by most zoonotic influenza virus infections, not all strains that can infect humans are able to transmit from person-to-person. Animal models of influenza are essential to research efforts aimed at understanding the viral and host factors that contribute to the disease and transmission outcomes of influenza virus infection in humans. These models furthermore allow the pre-clinical testing of antiviral drugs and vaccines aimed at reducing morbidity and mortality in the population through amelioration of the virulence or transmissibility of influenza viruses. Mice, ferrets, guinea pigs, cotton rats, hamsters and macaques have all been used to study influenza viruses and therapeutics targeting them. Each model presents unique advantages and disadvantages, which will be discussed herein.</p>
</abstract>
<kwd-group><kwd>influenza virus</kwd>
<kwd>transmission</kwd>
<kwd>pathogenicity</kwd>
<kwd>animal model</kwd>
<kwd>antiviral drug</kwd>
<kwd>influenza vaccine</kwd>
</kwd-group>
</article-meta>
</front>
<floats-group><table-wrap id="t1-viruses-02-01530" position="float"><label>Table 1.</label>
<caption><p>Susceptibility of standard inbred mice to influenza viruses following intranasal inoculation.</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" valign="top" rowspan="1" colspan="1"><bold>Viral Strain <xref ref-type="table-fn" rid="tfn1-viruses-02-01530">*</xref>
</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>50% infectious dose (LD<sub>50</sub>
) <xref ref-type="table-fn" rid="tfn2-viruses-02-01530">**</xref>
</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>50% lethal dose (LD<sub>50</sub>
) <xref ref-type="table-fn" rid="tfn2-viruses-02-01530">**</xref>
</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Mouse Strain</bold>
</th>
<th align="left" valign="top" rowspan="1" colspan="1"><bold>Reference</bold>
</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="bottom" rowspan="1" colspan="1">PR8 (H1N1)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1"></td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>2</sup>
PFU</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">BALB/C</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b40-viruses-02-01530">40</xref>
]</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">WSN (H1N1)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1"></td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>2</sup>
– 10<sup>3.3</sup>
PFU</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">BALB/C</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b40-viruses-02-01530">40</xref>
,<xref ref-type="bibr" rid="b74-viruses-02-01530">74</xref>
,<xref ref-type="bibr" rid="b75-viruses-02-01530">75</xref>
]</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">X31 (H3N2)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>0.7</sup>
EID<sub>50</sub>
</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">>10<sup>5.2</sup>
EID<sub>50</sub>
, 10<sup>5.84</sup>
PFU</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">BALB/C</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b40-viruses-02-01530">40</xref>
,<xref ref-type="bibr" rid="b48-viruses-02-01530">48</xref>
]</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">1918 pandemic strain (H1N1)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>0.75</sup>
PFU</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>3.25</sup>
to 10<sup>3.5</sup>
PFU</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">BALB/C</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b36-viruses-02-01530">36</xref>
,<xref ref-type="bibr" rid="b57-viruses-02-01530">57</xref>
]</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/New Caledonia/20/1999 (H1N1)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">∼10<sup>2.7</sup>
PFU</td>
<td align="left" valign="bottom" rowspan="1" colspan="1"></td>
<td align="left" valign="bottom" rowspan="1" colspan="1">C57BL/6</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b37-viruses-02-01530">37</xref>
]</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/Texas/36/1991 (H1N1)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1"></td>
<td align="left" valign="bottom" rowspan="1" colspan="1">>10<sup>6</sup>
PFU</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">BALB/C</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b36-viruses-02-01530">36</xref>
]</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/Kawasaki/UTK-4/09 (H1N1)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1"></td>
<td align="left" valign="bottom" rowspan="1" colspan="1">>10<sup>6.6</sup>
PFU</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">BALB/C</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b39-viruses-02-01530">39</xref>
]</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/Netherlands/607/2009 (pH1N1)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1"></td>
<td align="left" valign="bottom" rowspan="1" colspan="1"><10<sup>4.7</sup>
PFU</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">C57BL/6</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b73-viruses-02-01530">73</xref>
]</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/California/04/2009 (pH1N1)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>1.5</sup>
</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>4.7</sup>
to >10<sup>6</sup>
PFU</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">BALB/C</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b39-viruses-02-01530">39</xref>
,<xref ref-type="bibr" rid="b57-viruses-02-01530">57</xref>
,<xref ref-type="bibr" rid="b73-viruses-02-01530">73</xref>
]</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/Viet Nam/1203/2004 (H5N1)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>1.5</sup>
PFU, 10<sup>2.2</sup>
EID<sub>50</sub>
</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>1.3</sup>
PFU, 10<sup>1.8</sup>
EID<sub>50</sub>
</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">BALB/C</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b57-viruses-02-01530">57</xref>
,<xref ref-type="bibr" rid="b76-viruses-02-01530">76</xref>
]</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/Hong Kong/483/1997 (H5N1)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>2.2</sup>
EID<sub>50</sub>
</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>1.6</sup>
to 10<sup>2.4</sup>
EID<sub>50</sub>
</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">BALB/C</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b48-viruses-02-01530">48</xref>
,<xref ref-type="bibr" rid="b76-viruses-02-01530">76</xref>
]</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/chicken/BC/CN-7/04 (H7N3)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1"></td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>2.4</sup>
TCID<sub>50</sub>
</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">BALB/C</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b55-viruses-02-01530">55</xref>
]</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/Netherlands<bold>/</bold>
219/03 (H7N7)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>0.76</sup>
EID<sub>50</sub>
</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>2.5</sup>
EID<sub>50</sub>
, 10<sup>0.8</sup>
TCID<sub>50</sub>
</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">BALB/C</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b53-viruses-02-01530">53</xref>
,<xref ref-type="bibr" rid="b55-viruses-02-01530">55</xref>
]</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/turkey/VA/4529/02 (H7N2)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>1.76</sup>
EID<sub>50</sub>
</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">>10<sup>7</sup>
TCID<sub>50</sub>
</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">BALB/C</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b53-viruses-02-01530">53</xref>
]</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/Red Knot/NJ/1523470/06 (H7N3)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>1.5</sup>
PFU</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">>10<sup>4.8</sup>
PFU</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">BALB/C</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b56-viruses-02-01530">56</xref>
]</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/Ruddy Turnstone/DE/650645/02 (H2N9)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">10<sup>2.4</sup>
PFU</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">>10<sup>5.4</sup>
PFU</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">BALB/C</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">[<xref ref-type="bibr" rid="b56-viruses-02-01530">56</xref>
]</td>
</tr>
</tbody>
</table>
<table-wrap-foot><fn id="tfn1-viruses-02-01530"><label>*</label>
<p>pH1N1 indicates H1N1 subtype viruses of the 2009 pandemic</p>
</fn>
<fn id="tfn2-viruses-02-01530"><label>**</label>
<p>PFU = plaque forming units; EID<sub>50</sub>
= 50% egg infectious dose; TCID<sub>50</sub>
= 50% tissue culture infectious dose</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="t2-viruses-02-01530" position="float"><label>Table 2.</label>
<caption><p>Transmission of human influenza A viruses in hamsters. (Adapted from [<xref ref-type="bibr" rid="b179-viruses-02-01530">179</xref>
].)</p>
</caption>
<table frame="hsides" rules="groups"><thead><tr><th align="left" valign="bottom" rowspan="1" colspan="1"><bold>Virus</bold>
</th>
<th align="left" valign="bottom" rowspan="1" colspan="1"><bold>Maximum nasal wash titer [log<sub>10</sub>
50% egg-bit infectivity dose (EBID<sub>50</sub>
)/mL]</bold>
</th>
<th align="left" valign="bottom" rowspan="1" colspan="1"><bold>Transmission Efficiency [# transmissions/ # exposed, (%)]</bold>
</th>
</tr>
</thead>
<tbody><tr><td align="left" valign="bottom" rowspan="1" colspan="1"><italic>Virulent in humans</italic>
:</td>
<td align="left" valign="top" rowspan="1" colspan="1"></td>
<td align="left" valign="top" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/Finland/74 (H3N2)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">6.2</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">5/5 (100%)</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/Victoria/75 (H3N2)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">5.5</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">5/5, 6/6 (100%)</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/Texas/77 (H3N2)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">5.9</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">5/5, 4/5 (90%)</td>
</tr>
<tr><td colspan="3" align="left" valign="bottom" rowspan="1"><hr></hr>
</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1"><italic>Attenuated in humans</italic>
:</td>
<td align="left" valign="top" rowspan="1" colspan="1"></td>
<td align="left" valign="top" rowspan="1" colspan="1"></td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/PR/8/34 (H1N1)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">4.6</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">3/5 (60%)</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/Okuda/57 (H2N2)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">4.3</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">0/5, 0/5 (0%)</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/HK/l19/77 (H1N1)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">5.3</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">2/5 (40%)</td>
</tr>
<tr><td align="left" valign="bottom" rowspan="1" colspan="1">A/U.S.S.R./77 (H1N1)</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">5.3</td>
<td align="left" valign="bottom" rowspan="1" colspan="1">0/6, 0/5 (0%)</td>
</tr>
</tbody>
</table>
</table-wrap>
</floats-group>
</pmc>
<affiliations><list><country><li>États-Unis</li>
</country>
<region><li>État de New York</li>
</region>
</list>
<tree><country name="États-Unis"><region name="État de New York"><name sortKey="Bouvier, Nicole M" sort="Bouvier, Nicole M" uniqKey="Bouvier N" first="Nicole M." last="Bouvier">Nicole M. Bouvier</name>
</region>
<name sortKey="Lowen, Anice C" sort="Lowen, Anice C" uniqKey="Lowen A" first="Anice C." last="Lowen">Anice C. Lowen</name>
</country>
</tree>
</affiliations>
</record>
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