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The Membrane Protein of Severe Acute Respiratory Syndrome Coronavirus Acts as a Dominant Immunogen Revealed by a Clustering Region of Novel Functionally and Structurally Defined Cytotoxic T-Lymphocyte Epitopes

Identifieur interne : 002915 ( Main/Exploration ); précédent : 002914; suivant : 002916

The Membrane Protein of Severe Acute Respiratory Syndrome Coronavirus Acts as a Dominant Immunogen Revealed by a Clustering Region of Novel Functionally and Structurally Defined Cytotoxic T-Lymphocyte Epitopes

Auteurs : JUN LIU [République populaire de Chine] ; YEPING SUN [République populaire de Chine] ; JIANXUN QI [République populaire de Chine] ; FULIANG CHU [République populaire de Chine] ; HAO WU [République populaire de Chine] ; FENG GAO [République populaire de Chine] ; TAISHENG LI [République populaire de Chine] ; JINGHUA YAN [République populaire de Chine] ; George F. Gao [République populaire de Chine]

Source :

RBID : Pascal:10-0482639

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English descriptors

Abstract

Background. Severe acute respiratory syndrome coronavirus (SARS-CoV), which emerged with highly contagious and life-threatening characteristics in 2002, remains a potential risk for future outbreaks. Membrane (M) and envelope (E) proteins are major structural proteins of the SARS-CoV The M protein has been determined as a protective antigen in humoral responses. However, its potential roles in stimulating cellular immunity remain elusive. Methods. In this study, a panel of peptides derived from M and E proteins were tested by in vitro refolding, T2 cell-binding assays, and responses stimulated by cytotoxic T-lymphocyte (CTL) epitopes in HLA-A2.1/Kb transgenic mice and human peripheral blood mononuclear cells (PBMCs). Results. A nonameric epitope Mn2 and a decameric epitope Md3 derived from the M protein were identified and used for the evaluation of M protein-specific immunity. Responses stimulated by M protein-specific CTL epitopes have been found in the PBMCs of donors who had recovered from SARS infection. Additionally, the transmembrane domain of the M protein may contain a T cell epitope cluster revealed by the immunogenic and structural analysis of a panel of truncated peptides overlapping with Mn2 and Md3. Conclusions. The M protein of SARS-CoV holds dominant cellular immunogenicity. This, together with previous reports of a strong humoral response against the M protein, may help to further explain the immunogenicity of SARS and serves as potential targets for SARS-CoV vaccine design.


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<sZ>3 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences (CAS)</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<inist:fA14 i1="02">
<s1>Graduate University, CAS</s1>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Graduate University, CAS</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1">
<inist:fA14 i1="03">
<s1>China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, CAS</s1>
<s3>CHN</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology, Institute of Microbiology, CAS</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3">
<inist:fA14 i1="07">
<s1>Beijing Institutes of Life Science, CAS</s1>
<s2>Beijing</s2>
<s3>CHN</s3>
<sZ>9 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<placeName>
<settlement type="city">Pékin</settlement>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j" type="main">The Journal of infectious diseases</title>
<title level="j" type="abbreviated">J. infect. dis.</title>
<idno type="ISSN">0022-1899</idno>
<imprint>
<date when="2010">2010</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt>
<title level="j" type="main">The Journal of infectious diseases</title>
<title level="j" type="abbreviated">J. infect. dis.</title>
<idno type="ISSN">0022-1899</idno>
</seriesStmt>
</fileDesc>
<profileDesc>
<textClass>
<keywords scheme="KwdEn" xml:lang="en">
<term>Antigenic determinant</term>
<term>Coronavirus</term>
<term>Cytotoxic T lymphocyte</term>
<term>Cytotoxicity</term>
<term>Infection</term>
<term>Membrane protein</term>
<term>Severe acute respiratory syndrome</term>
<term>T-Lymphocyte</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr">
<term>Coronavirus</term>
<term>Protéine membranaire</term>
<term>Cytotoxicité</term>
<term>Lymphocyte T cytotoxique</term>
<term>Lymphocyte T</term>
<term>Déterminant antigénique</term>
<term>Infection</term>
<term>Syndrome respiratoire aigu sévère</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">Background. Severe acute respiratory syndrome coronavirus (SARS-CoV), which emerged with highly contagious and life-threatening characteristics in 2002, remains a potential risk for future outbreaks. Membrane (M) and envelope (E) proteins are major structural proteins of the SARS-CoV The M protein has been determined as a protective antigen in humoral responses. However, its potential roles in stimulating cellular immunity remain elusive. Methods. In this study, a panel of peptides derived from M and E proteins were tested by in vitro refolding, T2 cell-binding assays, and responses stimulated by cytotoxic T-lymphocyte (CTL) epitopes in HLA-A2.1/K
<sup>b</sup>
transgenic mice and human peripheral blood mononuclear cells (PBMCs). Results. A nonameric epitope Mn2 and a decameric epitope Md3 derived from the M protein were identified and used for the evaluation of M protein-specific immunity. Responses stimulated by M protein-specific CTL epitopes have been found in the PBMCs of donors who had recovered from SARS infection. Additionally, the transmembrane domain of the M protein may contain a T cell epitope cluster revealed by the immunogenic and structural analysis of a panel of truncated peptides overlapping with Mn2 and Md3. Conclusions. The M protein of SARS-CoV holds dominant cellular immunogenicity. This, together with previous reports of a strong humoral response against the M protein, may help to further explain the immunogenicity of SARS and serves as potential targets for SARS-CoV vaccine design.</div>
</front>
</TEI>
<affiliations>
<list>
<country>
<li>République populaire de Chine</li>
</country>
<settlement>
<li>Pékin</li>
</settlement>
</list>
<tree>
<country name="République populaire de Chine">
<noRegion>
<name sortKey="Jun Liu" sort="Jun Liu" uniqKey="Jun Liu" last="Jun Liu">JUN LIU</name>
</noRegion>
<name sortKey="Feng Gao" sort="Feng Gao" uniqKey="Feng Gao" last="Feng Gao">FENG GAO</name>
<name sortKey="Fuliang Chu" sort="Fuliang Chu" uniqKey="Fuliang Chu" last="Fuliang Chu">FULIANG CHU</name>
<name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
<name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
<name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
<name sortKey="Gao, George F" sort="Gao, George F" uniqKey="Gao G" first="George F." last="Gao">George F. Gao</name>
<name sortKey="Hao Wu" sort="Hao Wu" uniqKey="Hao Wu" last="Hao Wu">HAO WU</name>
<name sortKey="Jianxun Qi" sort="Jianxun Qi" uniqKey="Jianxun Qi" last="Jianxun Qi">JIANXUN QI</name>
<name sortKey="Jianxun Qi" sort="Jianxun Qi" uniqKey="Jianxun Qi" last="Jianxun Qi">JIANXUN QI</name>
<name sortKey="Jinghua Yan" sort="Jinghua Yan" uniqKey="Jinghua Yan" last="Jinghua Yan">JINGHUA YAN</name>
<name sortKey="Jinghua Yan" sort="Jinghua Yan" uniqKey="Jinghua Yan" last="Jinghua Yan">JINGHUA YAN</name>
<name sortKey="Jun Liu" sort="Jun Liu" uniqKey="Jun Liu" last="Jun Liu">JUN LIU</name>
<name sortKey="Jun Liu" sort="Jun Liu" uniqKey="Jun Liu" last="Jun Liu">JUN LIU</name>
<name sortKey="Taisheng Li" sort="Taisheng Li" uniqKey="Taisheng Li" last="Taisheng Li">TAISHENG LI</name>
<name sortKey="Yeping Sun" sort="Yeping Sun" uniqKey="Yeping Sun" last="Yeping Sun">YEPING SUN</name>
<name sortKey="Yeping Sun" sort="Yeping Sun" uniqKey="Yeping Sun" last="Yeping Sun">YEPING SUN</name>
<name sortKey="Yeping Sun" sort="Yeping Sun" uniqKey="Yeping Sun" last="Yeping Sun">YEPING SUN</name>
</country>
</tree>
</affiliations>
</record>

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