Prior immunization with severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein causes severe pneumonia in mice infected with SARS-CoV.
Identifieur interne : 003053 ( Main/Exploration ); précédent : 003052; suivant : 003054Prior immunization with severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein causes severe pneumonia in mice infected with SARS-CoV.
Auteurs : Fumihiko Yasui [Japon] ; Chieko Kai ; Masahiro Kitabatake ; Shingo Inoue ; Misako Yoneda ; Shoji Yokochi ; Ryoichi Kase ; Satoshi Sekiguchi ; Kouichi Morita ; Tsunekazu Hishima ; Hidenori Suzuki ; Katsuo Karamatsu ; Yasuhiro Yasutomi ; Hisatoshi Shida ; Minoru Kidokoro ; Kyosuke Mizuno ; Kouji Matsushima ; Michinori KoharaSource :
- Journal of immunology (Baltimore, Md. : 1950) [ 1550-6606 ] ; 2008.
Descripteurs français
- KwdFr :
- ARN messager (biosynthèse), Animaux, Anticorps antiviraux (biosynthèse), Cellules Vero, Cytokines (biosynthèse), Femelle, Humains, Indice de gravité médicale, Lapins, Lignée cellulaire, Pneumopathie virale (anatomopathologie), Pneumopathie virale (immunologie), Pneumopathie virale (virologie), Poumon (anatomopathologie), Poumon (immunologie), Poumon (virologie), Protéines nucléocapside (administration et posologie), Protéines nucléocapside (immunologie), Souris, Souris de lignée BALB C, Syndrome respiratoire aigu sévère (), Syndrome respiratoire aigu sévère (anatomopathologie), Syndrome respiratoire aigu sévère (virologie), Vaccins antiviraux (administration et posologie), Vaccins antiviraux (immunologie), Virus du SRAS (immunologie).
- MESH :
- administration et posologie : Protéines nucléocapside, Vaccins antiviraux.
- anatomopathologie : Pneumopathie virale, Poumon, Syndrome respiratoire aigu sévère.
- biosynthèse : ARN messager, Anticorps antiviraux, Cytokines.
- immunologie : Pneumopathie virale, Poumon, Protéines nucléocapside, Vaccins antiviraux, Virus du SRAS.
- virologie : Pneumopathie virale, Poumon, Syndrome respiratoire aigu sévère.
- Animaux, Cellules Vero, Femelle, Humains, Indice de gravité médicale, Lapins, Lignée cellulaire, Souris, Souris de lignée BALB C, Syndrome respiratoire aigu sévère.
English descriptors
- KwdEn :
- Animals, Antibodies, Viral (biosynthesis), Cell Line, Chlorocebus aethiops, Cytokines (biosynthesis), Female, Humans, Lung (immunology), Lung (pathology), Lung (virology), Mice, Mice, Inbred BALB C, Nucleocapsid Proteins (administration & dosage), Nucleocapsid Proteins (immunology), Pneumonia, Viral (immunology), Pneumonia, Viral (pathology), Pneumonia, Viral (virology), RNA, Messenger (biosynthesis), Rabbits, SARS Virus (immunology), Severe Acute Respiratory Syndrome (pathology), Severe Acute Respiratory Syndrome (prevention & control), Severe Acute Respiratory Syndrome (virology), Severity of Illness Index, Vero Cells, Viral Vaccines (administration & dosage), Viral Vaccines (immunology).
- MESH :
- chemical , administration & dosage : Nucleocapsid Proteins, Viral Vaccines.
- chemical , biosynthesis : Antibodies, Viral, Cytokines, RNA, Messenger.
- immunology : Lung, Nucleocapsid Proteins, Pneumonia, Viral, SARS Virus, Viral Vaccines.
- pathology : Lung, Pneumonia, Viral, Severe Acute Respiratory Syndrome.
- prevention & control : Severe Acute Respiratory Syndrome.
- virology : Lung, Pneumonia, Viral, Severe Acute Respiratory Syndrome.
- Animals, Cell Line, Chlorocebus aethiops, Female, Humans, Mice, Mice, Inbred BALB C, Rabbits, Severity of Illness Index, Vero Cells.
Abstract
The details of the mechanism by which severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes severe pneumonia are unclear. We investigated the immune responses and pathologies of SARS-CoV-infected BALB/c mice that were immunized intradermally with recombinant vaccinia virus (VV) that expressed either the SARS-CoV spike (S) protein (LC16m8rVV-S) or simultaneously all the structural proteins, including the nucleocapsid (N), membrane (M), envelope (E), and S proteins (LC16m8rVV-NMES) 7-8 wk before intranasal SARS-CoV infection. The LC16m8rVV-NMES-immunized group exhibited as severe pneumonia as the control groups, although LC16m8rVV-NMES significantly decreased the pulmonary SARS-CoV titer to the same extent as LC16m8rVV-S. To identify the cause of the exacerbated pneumonia, BALB/c mice were immunized with recombinant VV that expressed the individual structural proteins of SARS-CoV (LC16mOrVV-N, -M, -E, -S) with or without LC16mOrVV-S (i.e., LC16mOrVV-N, LC16mOrVV-M, LC16mOrVV-E, or LC16mOrVV-S alone or LC16mOrVV-N + LC16mOrVV-S, LC16mOrVV-M + LC16mOrVV-S, or LC16mOrVV-E + LC16mOrVV-S), and infected with SARS-CoV more than 4 wk later. Both LC16mOrVV-N-immunized mice and LC16mOrVV-N + LC16mOrVV-S-immunized mice exhibited severe pneumonia. Furthermore, LC16mOrVV-N-immunized mice upon infection exhibited significant up-regulation of both Th1 (IFN-gamma, IL-2) and Th2 (IL-4, IL-5) cytokines and down-regulation of anti-inflammatory cytokines (IL-10, TGF-beta), resulting in robust infiltration of neutrophils, eosinophils, and lymphocytes into the lung, as well as thickening of the alveolar epithelium. These results suggest that an excessive host immune response against the nucleocapsid protein of SARS-CoV is involved in severe pneumonia caused by SARS-CoV infection. These findings increase our understanding of the pathogenesis of SARS.
DOI: 10.4049/jimmunol.181.9.6337
PubMed: 18941225
Affiliations:
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Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Prior immunization with severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein causes severe pneumonia in mice infected with SARS-CoV.</title>
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<term>Chlorocebus aethiops</term>
<term>Cytokines (biosynthesis)</term>
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<front><div type="abstract" xml:lang="en">The details of the mechanism by which severe acute respiratory syndrome-associated coronavirus (SARS-CoV) causes severe pneumonia are unclear. We investigated the immune responses and pathologies of SARS-CoV-infected BALB/c mice that were immunized intradermally with recombinant vaccinia virus (VV) that expressed either the SARS-CoV spike (S) protein (LC16m8rVV-S) or simultaneously all the structural proteins, including the nucleocapsid (N), membrane (M), envelope (E), and S proteins (LC16m8rVV-NMES) 7-8 wk before intranasal SARS-CoV infection. The LC16m8rVV-NMES-immunized group exhibited as severe pneumonia as the control groups, although LC16m8rVV-NMES significantly decreased the pulmonary SARS-CoV titer to the same extent as LC16m8rVV-S. To identify the cause of the exacerbated pneumonia, BALB/c mice were immunized with recombinant VV that expressed the individual structural proteins of SARS-CoV (LC16mOrVV-N, -M, -E, -S) with or without LC16mOrVV-S (i.e., LC16mOrVV-N, LC16mOrVV-M, LC16mOrVV-E, or LC16mOrVV-S alone or LC16mOrVV-N + LC16mOrVV-S, LC16mOrVV-M + LC16mOrVV-S, or LC16mOrVV-E + LC16mOrVV-S), and infected with SARS-CoV more than 4 wk later. Both LC16mOrVV-N-immunized mice and LC16mOrVV-N + LC16mOrVV-S-immunized mice exhibited severe pneumonia. Furthermore, LC16mOrVV-N-immunized mice upon infection exhibited significant up-regulation of both Th1 (IFN-gamma, IL-2) and Th2 (IL-4, IL-5) cytokines and down-regulation of anti-inflammatory cytokines (IL-10, TGF-beta), resulting in robust infiltration of neutrophils, eosinophils, and lymphocytes into the lung, as well as thickening of the alveolar epithelium. These results suggest that an excessive host immune response against the nucleocapsid protein of SARS-CoV is involved in severe pneumonia caused by SARS-CoV infection. These findings increase our understanding of the pathogenesis of SARS.</div>
</front>
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<affiliations><list><country><li>Japon</li>
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<tree><noCountry><name sortKey="Hishima, Tsunekazu" sort="Hishima, Tsunekazu" uniqKey="Hishima T" first="Tsunekazu" last="Hishima">Tsunekazu Hishima</name>
<name sortKey="Inoue, Shingo" sort="Inoue, Shingo" uniqKey="Inoue S" first="Shingo" last="Inoue">Shingo Inoue</name>
<name sortKey="Kai, Chieko" sort="Kai, Chieko" uniqKey="Kai C" first="Chieko" last="Kai">Chieko Kai</name>
<name sortKey="Karamatsu, Katsuo" sort="Karamatsu, Katsuo" uniqKey="Karamatsu K" first="Katsuo" last="Karamatsu">Katsuo Karamatsu</name>
<name sortKey="Kase, Ryoichi" sort="Kase, Ryoichi" uniqKey="Kase R" first="Ryoichi" last="Kase">Ryoichi Kase</name>
<name sortKey="Kidokoro, Minoru" sort="Kidokoro, Minoru" uniqKey="Kidokoro M" first="Minoru" last="Kidokoro">Minoru Kidokoro</name>
<name sortKey="Kitabatake, Masahiro" sort="Kitabatake, Masahiro" uniqKey="Kitabatake M" first="Masahiro" last="Kitabatake">Masahiro Kitabatake</name>
<name sortKey="Kohara, Michinori" sort="Kohara, Michinori" uniqKey="Kohara M" first="Michinori" last="Kohara">Michinori Kohara</name>
<name sortKey="Matsushima, Kouji" sort="Matsushima, Kouji" uniqKey="Matsushima K" first="Kouji" last="Matsushima">Kouji Matsushima</name>
<name sortKey="Mizuno, Kyosuke" sort="Mizuno, Kyosuke" uniqKey="Mizuno K" first="Kyosuke" last="Mizuno">Kyosuke Mizuno</name>
<name sortKey="Morita, Kouichi" sort="Morita, Kouichi" uniqKey="Morita K" first="Kouichi" last="Morita">Kouichi Morita</name>
<name sortKey="Sekiguchi, Satoshi" sort="Sekiguchi, Satoshi" uniqKey="Sekiguchi S" first="Satoshi" last="Sekiguchi">Satoshi Sekiguchi</name>
<name sortKey="Shida, Hisatoshi" sort="Shida, Hisatoshi" uniqKey="Shida H" first="Hisatoshi" last="Shida">Hisatoshi Shida</name>
<name sortKey="Suzuki, Hidenori" sort="Suzuki, Hidenori" uniqKey="Suzuki H" first="Hidenori" last="Suzuki">Hidenori Suzuki</name>
<name sortKey="Yasutomi, Yasuhiro" sort="Yasutomi, Yasuhiro" uniqKey="Yasutomi Y" first="Yasuhiro" last="Yasutomi">Yasuhiro Yasutomi</name>
<name sortKey="Yokochi, Shoji" sort="Yokochi, Shoji" uniqKey="Yokochi S" first="Shoji" last="Yokochi">Shoji Yokochi</name>
<name sortKey="Yoneda, Misako" sort="Yoneda, Misako" uniqKey="Yoneda M" first="Misako" last="Yoneda">Misako Yoneda</name>
</noCountry>
<country name="Japon"><noRegion><name sortKey="Yasui, Fumihiko" sort="Yasui, Fumihiko" uniqKey="Yasui F" first="Fumihiko" last="Yasui">Fumihiko Yasui</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>
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