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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Differential Virological and Immunological Outcome of Severe Acute Respiratory Syndrome Coronavirus Infection in Susceptible and Resistant Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2<xref ref-type="fn" rid="fn1">▿</xref> </title><author><name sortKey="Yoshikawa, Naoko" sort="Yoshikawa, Naoko" uniqKey="Yoshikawa N" first="Naoko" last="Yoshikawa">Naoko Yoshikawa</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Yoshikawa, Tomoki" sort="Yoshikawa, Tomoki" uniqKey="Yoshikawa T" first="Tomoki" last="Yoshikawa">Tomoki Yoshikawa</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Hill, Terence" sort="Hill, Terence" uniqKey="Hill T" first="Terence" last="Hill">Terence Hill</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Huang, Cheng" sort="Huang, Cheng" uniqKey="Huang C" first="Cheng" last="Huang">Cheng Huang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Watts, Douglas M" sort="Watts, Douglas M" uniqKey="Watts D" first="Douglas M." last="Watts">Douglas M. Watts</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Makino, Shinji" sort="Makino, Shinji" uniqKey="Makino S" first="Shinji" last="Makino">Shinji Makino</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Milligan, Gregg" sort="Milligan, Gregg" uniqKey="Milligan G" first="Gregg" last="Milligan">Gregg Milligan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Chan, Tehsheng" sort="Chan, Tehsheng" uniqKey="Chan T" first="Tehsheng" last="Chan">Tehsheng Chan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Peters, Clarence J" sort="Peters, Clarence J" uniqKey="Peters C" first="Clarence J." last="Peters">Clarence J. Peters</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K." last="Tseng">Chien-Te K. Tseng</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">19297479</idno><idno type="pmc">2681954</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2681954</idno><idno type="RBID">PMC:2681954</idno><idno type="doi">10.1128/JVI.02272-08</idno><date when="2009">2009</date><idno type="wicri:Area/Pmc/Corpus">000671</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000671</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Differential Virological and Immunological Outcome of Severe Acute Respiratory Syndrome Coronavirus Infection in Susceptible and Resistant Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2<xref ref-type="fn" rid="fn1">▿</xref> </title><author><name sortKey="Yoshikawa, Naoko" sort="Yoshikawa, Naoko" uniqKey="Yoshikawa N" first="Naoko" last="Yoshikawa">Naoko Yoshikawa</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Yoshikawa, Tomoki" sort="Yoshikawa, Tomoki" uniqKey="Yoshikawa T" first="Tomoki" last="Yoshikawa">Tomoki Yoshikawa</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Hill, Terence" sort="Hill, Terence" uniqKey="Hill T" first="Terence" last="Hill">Terence Hill</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Huang, Cheng" sort="Huang, Cheng" uniqKey="Huang C" first="Cheng" last="Huang">Cheng Huang</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Watts, Douglas M" sort="Watts, Douglas M" uniqKey="Watts D" first="Douglas M." last="Watts">Douglas M. Watts</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Makino, Shinji" sort="Makino, Shinji" uniqKey="Makino S" first="Shinji" last="Makino">Shinji Makino</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Milligan, Gregg" sort="Milligan, Gregg" uniqKey="Milligan G" first="Gregg" last="Milligan">Gregg Milligan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Chan, Tehsheng" sort="Chan, Tehsheng" uniqKey="Chan T" first="Tehsheng" last="Chan">Tehsheng Chan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Peters, Clarence J" sort="Peters, Clarence J" uniqKey="Peters C" first="Clarence J." last="Peters">Clarence J. Peters</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Tseng, Chien Te K" sort="Tseng, Chien Te K" uniqKey="Tseng C" first="Chien-Te K." last="Tseng">Chien-Te K. Tseng</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></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="2009">2009</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>We previously reported that transgenic (Tg) mice expressing human angiotensin-converting enzyme 2 (hACE2), the receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), were highly susceptible to SARS-CoV infection, which resulted in the development of disease of various severity and even death in some lineages. In this study, we further characterized and compared the pathogeneses of SARS-CoV infection in two of the most stable Tg lineages, AC70 and AC22, representing those susceptible and resistant to the lethal SARS-CoV infection, respectively. The kinetics of virus replication and the inflammatory responses within the lungs and brains, as well as the clinical and pathological outcomes, were assessed in each lineage. In addition, we generated information on lymphocyte subsets and mitogen-mediated proliferation of splenocytes. We found that while both lineages were permissive to SARS-CoV infection, causing elevated secretion of many inflammatory mediators within the lungs and brains, viral infection appeared to be more intense in AC70 than in AC22 mice, especially in the brain. Moreover, such infection was accompanied by a more profound immune suppression in the former, as evidenced by the extensive loss of T cells, compromised responses to concanavalin A stimulation, and absence of inflammatory infiltrates within the brain. We also found that CD8<sup>+</sup> T cells were partially effective in attenuating the pathogenesis of SARS-CoV infection in lethality-resistant AC22 mice. Collectively, our data revealed a more intense viral infection and immunosuppression in AC70 mice than in AC22 mice, thereby providing us with an immunopathogenic basis for the fatal outcome of SARS-CoV infection in the AC70 mice.</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="publisher-id">jvi</journal-id><journal-title>Journal of Virology</journal-title><issn pub-type="ppub">0022-538X</issn><issn pub-type="epub">1098-5514</issn><publisher><publisher-name>American Society for Microbiology (ASM)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">19297479</article-id><article-id pub-id-type="pmc">2681954</article-id><article-id pub-id-type="publisher-id">2272-08</article-id><article-id pub-id-type="doi">10.1128/JVI.02272-08</article-id><article-categories><subj-group subj-group-type="heading"><subject>Pathogenesis and Immunity</subject></subj-group></article-categories><title-group><article-title>Differential Virological and Immunological Outcome of Severe Acute Respiratory Syndrome Coronavirus Infection in Susceptible and Resistant Transgenic Mice Expressing Human Angiotensin-Converting Enzyme 2<xref ref-type="fn" rid="fn1">▿</xref> </article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Yoshikawa</surname><given-names>Naoko</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Yoshikawa</surname><given-names>Tomoki</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Hill</surname><given-names>Terence</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Huang</surname><given-names>Cheng</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Watts</surname><given-names>Douglas M.</given-names></name><xref ref-type="aff" rid="aff1">2</xref></contrib><contrib contrib-type="author"><name><surname>Makino</surname><given-names>Shinji</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Milligan</surname><given-names>Gregg</given-names></name><xref ref-type="aff" rid="aff1">3</xref></contrib><contrib contrib-type="author"><name><surname>Chan</surname><given-names>Tehsheng</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Peters</surname><given-names>Clarence J.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff1">2</xref><xref ref-type="aff" rid="aff1">4</xref></contrib><contrib contrib-type="author"><name><surname>Tseng</surname><given-names>Chien-Te K.</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff1">4</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="aff1">Departments of Microbiology and Immunology,<label>1</label> Pathology,<label>2</label> Pediatrics,<label>3</label> Center for Biodefense and Emerging Infectious Disease, University of Texas Medical Branch, Galveston, Texas 77555-0609<label>4</label></aff><author-notes><fn id="cor1"><label>*</label><p>Corresponding author. Mailing address: Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Boulevard, G.150 Keiller Building, Galveston, TX 77555-0609. Phone: (409) 747-0789. Fax: (409) 747-0762. E-mail: <email>sktseng@utmb.edu</email></p></fn></author-notes><pub-date pub-type="ppub"><month>6</month><year>2009</year></pub-date><pub-date pub-type="epub"><day>18</day><month>3</month><year>2009</year></pub-date><volume>83</volume><issue>11</issue><fpage>5451</fpage><lpage>5465</lpage><history><date date-type="received"><day>29</day><month>10</month><year>2008</year></date><date date-type="accepted"><day>10</day><month>3</month><year>2009</year></date></history><permissions><copyright-statement>Copyright © 2009, American Society for Microbiology</copyright-statement></permissions><self-uri xlink:title="pdf" xlink:href="zjv01109005451.pdf"></self-uri><abstract><p>We previously reported that transgenic (Tg) mice expressing human angiotensin-converting enzyme 2 (hACE2), the receptor for severe acute respiratory syndrome coronavirus (SARS-CoV), were highly susceptible to SARS-CoV infection, which resulted in the development of disease of various severity and even death in some lineages. In this study, we further characterized and compared the pathogeneses of SARS-CoV infection in two of the most stable Tg lineages, AC70 and AC22, representing those susceptible and resistant to the lethal SARS-CoV infection, respectively. The kinetics of virus replication and the inflammatory responses within the lungs and brains, as well as the clinical and pathological outcomes, were assessed in each lineage. In addition, we generated information on lymphocyte subsets and mitogen-mediated proliferation of splenocytes. We found that while both lineages were permissive to SARS-CoV infection, causing elevated secretion of many inflammatory mediators within the lungs and brains, viral infection appeared to be more intense in AC70 than in AC22 mice, especially in the brain. Moreover, such infection was accompanied by a more profound immune suppression in the former, as evidenced by the extensive loss of T cells, compromised responses to concanavalin A stimulation, and absence of inflammatory infiltrates within the brain. We also found that CD8<sup>+</sup> T cells were partially effective in attenuating the pathogenesis of SARS-CoV infection in lethality-resistant AC22 mice. Collectively, our data revealed a more intense viral infection and immunosuppression in AC70 mice than in AC22 mice, thereby providing us with an immunopathogenic basis for the fatal outcome of SARS-CoV infection in the AC70 mice.</p></abstract></article-meta></front><floats-wrap><fig position="float" id="f1"><label>FIG. 1.</label><caption><p>Tissue expression profile of hACE2 in the Tg mouse lineages AC70 (A) and AC22 (B). DNA-free RNAs extracted from different organs of Tg mice at 6 to 8 weeks of age were subjected to RT-PCR analysis to evaluate the expression of hACE2 mRNA. The RT-PCR products were analyzed on 2% agarose gels. The data shown are representative of two independently conducted experiments.</p></caption><graphic xlink:href="zjv0110919240001"></graphic></fig><fig position="float" id="f2"><label>FIG. 2.</label><caption><p>Differential outcomes of SARS-CoV infection in AC70 and AC22 Tg mice. Groups of hACE2 Tg and age-matched non-Tg mice (control) (<italic>n</italic> = 14 to 31 mice/group) were infected intranasally with 10<sup>6</sup> TCID<sub>50</sub> of SARS-CoV (Urbani strain). The severity of clinical illness, i.e., weight loss (A), average illness score (B), and cumulative mortality (C), of infected mice was recorded daily as described in Materials and Methods. Error bars indicate standard deviations.</p></caption><graphic xlink:href="zjv0110919240002"></graphic></fig><fig position="float" id="f3"><label>FIG. 3.</label><caption><p>Kinetics of viral replication in the lungs and brains of SARS-CoV-infected AC70 and AC22 mice. AC70 (A) and AC22 (B) mice were infected with SARS-CoV as described for Fig. <xref rid="f1" ref-type="fig">1</xref>. Three mice from each group were sacrificed at the indicated days after infection for determining infectious virus titers in the lungs and brains by the standard infectivity assay in Vero E6 cells. The viral titers were expressed as log<sub>10</sub> TCID<sub>50</sub> virus per gram of tissue. Data are shown as means ± standard deviations for three animals at each time point, except for AC70 mice at day 5, where only one mouse survived the infection.</p></caption><graphic xlink:href="zjv0110919240003"></graphic></fig><fig position="float" id="f4"><label>FIG. 4.</label><caption><p>SARS-CoV antigen expression in the lungs of AC70 and AC22 mice. Paraffin-embedded lung sections of SARS-CoV-infected AC70 mice (A to C) and AC22 mice (D to F) were analyzed for the expression of SARS-CoV nucleocapsid protein by IHC, as described in Materials and Methods. Profound viral infection, as indicated by the intense staining of viral antigen (red), was first detected in the cytoplasm of bronchial epithelial cells (A and D) at day 1, subsequently spread to the alveolar epithelial cells at day 2 (B and E), and subsided to either an undetectable level (C) or a lower level (F) in AC70 and AC22 mice at day 3, respectively. Original magnifications, ×40.</p></caption><graphic xlink:href="zjv0110919240004"></graphic></fig><fig position="float" id="f5"><label>FIG. 5.</label><caption><p>SARS-CoV antigen expression in the brains of AC70 and AC22 mice. The brains of infected AC70 (A to C) and AC22 (D to F) mice were fixed, sectioned, and processed for the staining of SARS-CoV N protein as for Fig. <xref rid="f3" ref-type="fig">3</xref>. Viral antigen could be consistently detected in many neuronal cells of AC70 mice from day 3 (A) and remained readily detectable at days 4 and 5 (B and C). The earliest time for detecting viral antigen in the neuronal cells of infected AC22 mice was day 4 (D), and it remained detectable at days 6 and 10 after infection (E and F). Original magnifications, ×40.</p></caption><graphic xlink:href="zjv0110919240005"></graphic></fig><fig position="float" id="f6"><label>FIG. 6.</label><caption><p>Lung pathology of SARS-CoV-infected AC70 and AC22 mice. We examined paraffin-embedded, hematoxylin- and eosin-stained lung sections obtained from mock-infected (A) and SARS-CoV-infected AC70 (B to F) and AC22 (G to K) mice at the indicated time points after infection. Lung pathology in both lineages started at 1 day p.i. (dpi) (with mild mononuclear cell infiltration around blood vessels and bronchioles, accompanied by swelling and blebbing of epithelial cells of bronchi and bronchioles (B and G). Accumulation of cell debris within the lumen (arrow), interstitial thickening, and inflammatory cellular infiltrates were observed at day 2 (C and H). Peribronchial inflammation continued, as the damaged pneumocytes and disrupted epithelial lining were readily detectable through days 3 and 4 (B, I, E, and J) and gradually subsided thereafter, with a minimal-to-mild cellular infiltration observed at day 5 (F and K). Original magnifications, ×20.</p></caption><graphic xlink:href="zjv0110919240006"></graphic></fig><fig position="float" id="f7"><label>FIG. 7.</label><caption><p>Brain pathology of SARS-CoV-infected AC70 and AC22 mice. Brains harvested from infected mice daily from day 1 to 5 for both hACE2 lineages and every 3 to 4 days thereafter were paraffin embedded, sectioned, and stained with hematoxylin and eosin. No obvious brain pathology was observed prior to days 3 and 4 in infected AC70 and AC22 mice, respectively. Perivascular cuffing in the meninge was observed only in a single infected AC70 mouse at day 3 (A). Very little pathology, if any, could be detected in the brains of infected AC70 mice thereafter (B [day 4] and C [day 5]). In contrast, perivacular cuffing was consistently detected in all infected AC22 mice, starting at day 4 (D). A time-dependent and prominent inflammatory infiltration was observed at day 6 (E). Perivascular cuffing persisted through day 21 (F), when the study was terminated. Original magnifications, ×20.</p></caption><graphic xlink:href="zjv0110919240007"></graphic></fig><fig position="float" id="f8"><label>FIG. 8.</label><caption><p>Kinetics of the cytokine responses in the lungs of SARS-CoV-infected AC70 and AC22 mice. Lung homogenates derived from AC70 and AC22 mice at the indicated time points after infection were used to assess the levels of chemokines and cytokines by Bio-Plex analysis. Duplicate samples of individual specimens were assayed. Results are shown as means ± standard deviations for three animals at the indicated time points, except for day 5, at which only two AC70 mice that survived the infection were used. *, <italic>P</italic> < 0.05; **, <italic>P</italic> < 0.01 (Student's <italic>t</italic> test, compared to mock-infected mice).</p></caption><graphic xlink:href="zjv0110919240008"></graphic></fig><fig position="float" id="f9"><label>FIG. 9.</label><caption><p>Kinetics of the cytokine responses in the brains of SARS-CoV-infected AC70 and AC22 mice. Homogenates of the brains harvested from AC70 and AC22 mice at the indicated time points after SARS-CoV infection were used to measure the expression of various cytokines and chemokines by Bio-Plex analysis. Duplicate samples of individual specimens were assayed. Results are shown as means ± standard deviations for three animals at the indicated time points, except for day 5, at which only two AC70 mice that survived the infection were used. *, <italic>P</italic> < 0.05; **, <italic>P</italic> < 0.01 (Student's <italic>t</italic> test, compared to mock-infected mice).</p></caption><graphic xlink:href="zjv011091924009a"></graphic><graphic xlink:href="zjv011091924009b"></graphic></fig><fig position="float" id="f10"><label>FIG. 10.</label><caption><p>SARS-CoV significantly inhibits ConA-mediated proliferation of T cells in infected AC70 and AC22 mice. AC70 and AC22 mice were either uninfected or infected (i.n.) with 10<sup>6</sup> TCID<sub>50</sub> SARS-CoV. Splenocytes were prepared from individual mice and tested for their proliferation in response to ConA (2.5 μg/ml) stimulation, as described in Materials and Methods. Student's <italic>t</italic> test was used to determine the <italic>P</italic> values between the indicated groups for statistical significance. N.S., not significant. Error bars indicate standard deviations.</p></caption><graphic xlink:href="zjv0110919240010"></graphic></fig><fig position="float" id="f11"><label>FIG. 11.</label><caption><p>Exacerbated pathogenesis of SARS-CoV infection in CD8-depleted Tg AC22 mice. Two groups of Tg AC22 mice (12 mice per group) were subjected to multiple doses (i.p.) of rat anti-mouse CD8 monoclonal antibody and an isotype-matched irrelevant rat monoclonal antibody (as control), respectively, as described in Materials and Methods. They were then infected i.n. with 10<sup>6</sup> TCID<sub>50</sub> SARS-CoV. Two mice/group were sacrificed after two doses of antibody treatment for assessing by flow cytometry the efficacy of antibody-mediated CD8 depletion in the spleens, whereas the effect of CD8 depletion on the pathogenesis of SARS-CoV infection was evaluated by virologic, clinical, and pathological parameters, as described in the text. Briefly, two additional mice were sacrificed at days 2 and 4 p.i. to allow assessment of virus infectivity and pathology in the lungs and brains, and the remaining mice were monitored for the onset of illness (i.e., weight loss). It appeared that a two-dose specific-antibody treatment regimen effectively depleted most of the CD8<sup>+</sup> T cells from the spleens (A). SARS-CoV infection of CD8-depleted mice resulted in increased infection in the lungs, but not in the brains, at both days 2 and 4 p.i. (B). This was accompanied by an increased weight loss (C), as well as more pronounced histopathology and the retention of viral NC antigen at day 4 p.i., as revealed by hematoxylin and eosin staining and IHC, respectively (D).</p></caption><graphic xlink:href="zjv0110919240011"></graphic></fig><table-wrap position="float" id="t1"><label>TABLE 1.</label><caption><p>Differential outcome of hACE2 Tg mouse lineage to SARS-CoV infection</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="1" align="center" valign="bottom">Transgenic lineage</th><th colspan="1" rowspan="1" align="center" valign="bottom">TCID<sub>50</sub> (log<sub>10</sub>) of SARS-CoV (Urbani strain)</th><th colspan="1" rowspan="1" align="center" valign="bottom">Morbidity (weight loss, etc.)</th><th colspan="1" rowspan="1" align="center" valign="bottom">Mortality (%)</th><th colspan="1" rowspan="1" align="center" valign="bottom">Mean survival time (days p.i.)</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">AC70</td><td colspan="1" rowspan="1" align="char" char="." valign="top">3</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="char" char="." valign="top">100</td><td colspan="1" rowspan="1" align="center" valign="top">6.2</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">AC50</td><td colspan="1" rowspan="1" align="char" char="." valign="top">3</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="char" char="." valign="top">100</td><td colspan="1" rowspan="1" align="center" valign="top">6.9</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">AC12</td><td colspan="1" rowspan="1" align="char" char="." valign="top">3</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="char" char="." valign="top">100</td><td colspan="1" rowspan="1" align="center" valign="top">4.5</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">AC22</td><td colspan="1" rowspan="1" align="char" char="." valign="top">6</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0</td><td colspan="1" rowspan="1" align="center" valign="top">—<xref ref-type="table-fn" rid="t1fn1"><italic>a</italic></xref></td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">AC63</td><td colspan="1" rowspan="1" align="char" char="." valign="top">6</td><td colspan="1" rowspan="1" align="center" valign="top">+</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0</td><td colspan="1" rowspan="1" align="center" valign="top">—</td></tr></tbody></table><table-wrap-foot><fn id="t1fn1"><label>a</label><p>—, not applicable.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t2"><label>TABLE 2.</label><caption><p>Total cell counts and lymphocyte subsets in the spleens of SARS-CoA-infected AC70 and AC22 mice and mock-infected control mice</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="4" align="center" valign="middle">Cells</th><th colspan="5" rowspan="1" align="center" valign="bottom">AC22 mice
<hr></hr></th><th colspan="5" rowspan="1" align="center" valign="bottom">AC70 mice
<hr></hr></th></tr><tr><th colspan="4" rowspan="1" align="center" valign="bottom">No. of cells (10<sup>6</sup>) or ratio<xref ref-type="table-fn" rid="t2fn1"><italic>a</italic></xref><hr></hr></th><th colspan="1" rowspan="3" align="center" valign="middle"><italic>P</italic><xref ref-type="table-fn" rid="t2fn2"><italic>b</italic></xref></th><th colspan="4" rowspan="1" align="center" valign="bottom">No. of cells (10<sup>6</sup>) or ratio
<hr></hr></th><th colspan="1" rowspan="3" align="center" valign="middle"><italic>P</italic></th></tr><tr><th colspan="2" rowspan="1" align="center" valign="bottom">Mock infection
<hr></hr></th><th colspan="2" rowspan="1" align="center" valign="bottom">SARS infection
<hr></hr></th><th colspan="2" rowspan="1" align="center" valign="bottom">Mock infection
<hr></hr></th><th colspan="2" rowspan="1" align="center" valign="bottom">SARS infection
<hr></hr></th></tr><tr><th colspan="1" rowspan="1" align="center" valign="bottom">Mean</th><th colspan="1" rowspan="1" align="center" valign="bottom">SD</th><th colspan="1" rowspan="1" align="center" valign="bottom">Mean</th><th colspan="1" rowspan="1" align="center" valign="bottom">SD</th><th colspan="1" rowspan="1" align="center" valign="bottom">Mean</th><th colspan="1" rowspan="1" align="center" valign="bottom">SD</th><th colspan="1" rowspan="1" align="center" valign="bottom">Mean</th><th colspan="1" rowspan="1" align="center" valign="bottom">SD</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">Splenocytes</td><td colspan="1" rowspan="1" align="char" char="." valign="top">130.0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">10.0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">130.0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">10.0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.698</td><td colspan="1" rowspan="1" align="char" char="." valign="top">166.7</td><td colspan="1" rowspan="1" align="char" char="." valign="top">11.5</td><td colspan="1" rowspan="1" align="char" char="." valign="top">100.0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">28.3</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.032</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">CD4 cells</td><td colspan="1" rowspan="1" align="char" char="." valign="top">41.4</td><td colspan="1" rowspan="1" align="char" char="." valign="top">2.5</td><td colspan="1" rowspan="1" align="char" char="." valign="top">25.4</td><td colspan="1" rowspan="1" align="char" char="." valign="top">2.7</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.005</td><td colspan="1" rowspan="1" align="char" char="." valign="top">52.3</td><td colspan="1" rowspan="1" align="char" char="." valign="top">3.9</td><td colspan="1" rowspan="1" align="char" char="." valign="top">32.1</td><td colspan="1" rowspan="1" align="char" char="." valign="top">7.5</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.025</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">CD8 cells</td><td colspan="1" rowspan="1" align="char" char="." valign="top">19.9</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.7</td><td colspan="1" rowspan="1" align="char" char="." valign="top">18.1</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4.2</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.652</td><td colspan="1" rowspan="1" align="char" char="." valign="top">31.0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1.9</td><td colspan="1" rowspan="1" align="char" char="." valign="top">7.0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.1</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.001</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">CD4/CD8 ratio</td><td colspan="1" rowspan="1" align="char" char="." valign="top">2.1</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1.4</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.3</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.095</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1.7</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.2</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4.6</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1.2</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.018</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">B cells</td><td colspan="1" rowspan="1" align="char" char="." valign="top">49.4</td><td colspan="1" rowspan="1" align="char" char="." valign="top">2.9</td><td colspan="1" rowspan="1" align="char" char="." valign="top">58.7</td><td colspan="1" rowspan="1" align="char" char="." valign="top">9.4</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.278</td><td colspan="1" rowspan="1" align="char" char="." valign="top">58.1</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1.0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">43.5</td><td colspan="1" rowspan="1" align="char" char="." valign="top">9.6</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.060</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">Non-T non-B cells</td><td colspan="1" rowspan="1" align="char" char="." valign="top">24.3</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1.0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">27.9</td><td colspan="1" rowspan="1" align="char" char="." valign="top">7.5</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.599</td><td colspan="1" rowspan="1" align="char" char="." valign="top">25.2</td><td colspan="1" rowspan="1" align="char" char="." valign="top">8.7</td><td colspan="1" rowspan="1" align="char" char="." valign="top">17.4</td><td colspan="1" rowspan="1" align="char" char="." valign="top">11.4</td><td colspan="1" rowspan="1" align="char" char="." valign="top">0.414</td></tr></tbody></table><table-wrap-foot><fn id="t2fn1"><label>a</label><p>Means and standard deviations are for three or four mice.</p></fn><fn id="t2fn2"><label>b</label><p>Student's <italic>t</italic> test for mock-infected versus infected mice.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="t3"><label>TABLE 3.</label><caption><p>ConA-stimulated proliferation of splenic T cells in uninfected and SARS-CoV-infected AC70 and AC22 mice</p></caption><table frame="hsides" rules="groups"><thead><tr><th colspan="1" rowspan="4" align="center" valign="middle">Mice</th><th colspan="6" rowspan="1" align="center" valign="bottom">Mock infection
<hr></hr></th><th colspan="6" rowspan="1" align="center" valign="bottom">SARS-CoV infection
<hr></hr></th></tr><tr><th colspan="4" rowspan="1" align="center" valign="bottom">[<sup>3</sup>H]thymidine uptake (cpm)
<hr></hr></th><th colspan="2" rowspan="2" align="center" valign="bottom">SI<xref ref-type="table-fn" rid="t3fn1"><italic>a</italic></xref><hr></hr></th><th colspan="4" rowspan="1" align="center" valign="bottom">[<sup>3</sup>H]thymidine uptake (cpm)
<hr></hr></th><th colspan="2" rowspan="2" align="center" valign="bottom">SI
<hr></hr></th></tr><tr><th colspan="2" rowspan="1" align="center" valign="bottom">Stimulated cultures
<hr></hr></th><th colspan="2" rowspan="1" align="center" valign="bottom">Unstimulated cultures
<hr></hr></th><th colspan="2" rowspan="1" align="center" valign="bottom">Stimulated cultures
<hr></hr></th><th colspan="2" rowspan="1" align="center" valign="bottom">Unstimulated cultures
<hr></hr></th></tr><tr><th colspan="1" rowspan="1" align="center" valign="bottom">Mean</th><th colspan="1" rowspan="1" align="center" valign="bottom">SD</th><th colspan="1" rowspan="1" align="center" valign="bottom">Mean</th><th colspan="1" rowspan="1" align="center" valign="bottom">SD</th><th colspan="1" rowspan="1" align="center" valign="bottom">Mean</th><th colspan="1" rowspan="1" align="center" valign="bottom">SD</th><th colspan="1" rowspan="1" align="center" valign="bottom">Mean</th><th colspan="1" rowspan="1" align="center" valign="bottom">SD</th><th colspan="1" rowspan="1" align="center" valign="bottom">Mean</th><th colspan="1" rowspan="1" align="center" valign="bottom">SD</th><th colspan="1" rowspan="1" align="center" valign="bottom">Mean</th><th colspan="1" rowspan="1" align="center" valign="bottom">SD</th></tr></thead><tbody><tr><td colspan="1" rowspan="1" align="left" valign="top">AC70</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4,370</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1,790</td><td colspan="1" rowspan="1" align="char" char="." valign="top">86</td><td colspan="1" rowspan="1" align="char" char="." valign="top">39</td><td colspan="1" rowspan="1" align="char" char="." valign="top">54</td><td colspan="1" rowspan="1" align="char" char="." valign="top">27</td><td colspan="1" rowspan="1" align="char" char="." valign="top">552</td><td colspan="1" rowspan="1" align="char" char="." valign="top">246</td><td colspan="1" rowspan="1" align="char" char="." valign="top">138</td><td colspan="1" rowspan="1" align="char" char="." valign="top">138</td><td colspan="1" rowspan="1" align="char" char="." valign="top">6.0</td><td colspan="1" rowspan="1" align="char" char="." valign="top">3</td></tr><tr><td colspan="1" rowspan="1" align="left" valign="top">AC22</td><td colspan="1" rowspan="1" align="char" char="." valign="top">4,700</td><td colspan="1" rowspan="1" align="char" char="." valign="top">725</td><td colspan="1" rowspan="1" align="char" char="." valign="top">68</td><td colspan="1" rowspan="1" align="char" char="." valign="top">14</td><td colspan="1" rowspan="1" align="char" char="." valign="top">70</td><td colspan="1" rowspan="1" align="char" char="." valign="top">15</td><td colspan="1" rowspan="1" align="char" char="." valign="top">1,845</td><td colspan="1" rowspan="1" align="char" char="." valign="top">841</td><td colspan="1" rowspan="1" align="char" char="." valign="top">83</td><td colspan="1" rowspan="1" align="char" char="." valign="top">19</td><td colspan="1" rowspan="1" align="char" char="." valign="top">24</td><td colspan="1" rowspan="1" align="char" char="." valign="top">13</td></tr></tbody></table><table-wrap-foot><fn id="t3fn1"><label>a</label><p>SI, stimulation index (cpm of ConA-stimulated cultures/cpm of unstimulated cultures).</p></fn></table-wrap-foot></table-wrap></floats-wrap></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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