A Functional Variation in CD55 Increases the Severity of 2009 Pandemic H1N1 Influenza A Virus Infection
Identifieur interne : 002237 ( Main/Curation ); précédent : 002236; suivant : 002238A Functional Variation in CD55 Increases the Severity of 2009 Pandemic H1N1 Influenza A Virus Infection
Auteurs : JIE ZHOU [Hong Kong] ; Kelvin Kai-Wang To [Hong Kong] ; HUI DONG [République populaire de Chine] ; Zhong-Shan Cheng [Hong Kong] ; Candy Choi-Yi Lau [Hong Kong] ; Vincent K. M. Poon [Hong Kong] ; Yan-Hui Fan [Hong Kong] ; You-Qiang Song [Hong Kong] ; Herman Tse [Hong Kong] ; Kwok-Hung Chan [Hong Kong] ; Bo-Jian Zheng [Hong Kong] ; Guo-Ping Zhao [République populaire de Chine] ; Kwok-Yung Yuen [Hong Kong]Source :
- The Journal of infectious diseases [ 0022-1899 ] ; 2012.
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Abstract
Infection due to 2009 pandemic H1N1 influenza A virus (A[H1N1]pdm09) is commonly manifested as mild infection but occasionally as severe pneumonia. We hypothesized that host genetic variations may contribute to disease severity. An initially small-scale genome-wide association study guided the selection of CD55 single-nucleotide polymorphisms in 425 Chinese patients with severe (n = 177) or mild (n = 248) disease. Carriers of rs2564978 genotype T/T were significantly associated with severe infection (odds ratio, 1.75; P = .011) under a recessive model, after adjustment for clinical confounders. An allele-specific effect on CD55 expression was revealed and ascribed to a promoter indel variation, which was in complete linkage disequilibrium with rs2564978. The promoter variant with deletion exhibited significantly lower transcriptional activity. We further demonstrated that CD55 can protect respiratory epithelial cells from complement attack. Additionally, A(H1N1)pdm09 infection promoted CD55 expression. In conclusion, CD55 polymorphisms are associated with severe A(H1N1)pdm09 infection. CD55 may exert a substantial impact on the disease severity of A (H1N1)pdm09 infection.
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">A Functional Variation in CD55 Increases the Severity of 2009 Pandemic H1N1 Influenza A Virus Infection</title>
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<wicri:noRegion>Carol Yu Center for Infection, The University of Hong Kong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hui Dong" sort="Hui Dong" uniqKey="Hui Dong" last="Hui Dong">HUI DONG</name>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Chinese National Human Genome Center at Shanghai</s1>
<s3>CHN</s3>
<sZ>3 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Chinese National Human Genome Center at Shanghai</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Cheng, Zhong Shan" sort="Cheng, Zhong Shan" uniqKey="Cheng Z" first="Zhong-Shan" last="Cheng">Zhong-Shan Cheng</name>
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<s3>HKG</s3>
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<sZ>13 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Department of Microbiology, The University of Hong Kong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lau, Candy Choi Yi" sort="Lau, Candy Choi Yi" uniqKey="Lau C" first="Candy Choi-Yi" last="Lau">Candy Choi-Yi Lau</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology, The University of Hong Kong</s1>
<s3>HKG</s3>
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<sZ>13 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Department of Microbiology, The University of Hong Kong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Poon, Vincent K M" sort="Poon, Vincent K M" uniqKey="Poon V" first="Vincent K. M." last="Poon">Vincent K. M. Poon</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology, The University of Hong Kong</s1>
<s3>HKG</s3>
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<sZ>4 aut.</sZ>
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<sZ>11 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Department of Microbiology, The University of Hong Kong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Fan, Yan Hui" sort="Fan, Yan Hui" uniqKey="Fan Y" first="Yan-Hui" last="Fan">Yan-Hui Fan</name>
<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Biochemistry, The University of Hong Kong</s1>
<s3>HKG</s3>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Department of Biochemistry, The University of Hong Kong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Song, You Qiang" sort="Song, You Qiang" uniqKey="Song Y" first="You-Qiang" last="Song">You-Qiang Song</name>
<affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Biochemistry, The University of Hong Kong</s1>
<s3>HKG</s3>
<sZ>7 aut.</sZ>
<sZ>8 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Department of Biochemistry, The University of Hong Kong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Tse, Herman" sort="Tse, Herman" uniqKey="Tse H" first="Herman" last="Tse">Herman Tse</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology, The University of Hong Kong</s1>
<s3>HKG</s3>
<sZ>1 aut.</sZ>
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<country>Hong Kong</country>
<wicri:noRegion>Department of Microbiology, The University of Hong Kong</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research Center of Infection and Immunology, The University of Hong Kong</s1>
<s3>HKG</s3>
<sZ>1 aut.</sZ>
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<sZ>10 aut.</sZ>
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<country>Hong Kong</country>
<wicri:noRegion>Research Center of Infection and Immunology, The University of Hong Kong</wicri:noRegion>
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<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong</s1>
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<sZ>2 aut.</sZ>
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<sZ>10 aut.</sZ>
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<sZ>13 aut.</sZ>
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<country>Hong Kong</country>
<wicri:noRegion>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Carol Yu Center for Infection, The University of Hong Kong</s1>
<s3>HKG</s3>
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<country>Hong Kong</country>
<wicri:noRegion>Carol Yu Center for Infection, The University of Hong Kong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chan, Kwok Hung" sort="Chan, Kwok Hung" uniqKey="Chan K" first="Kwok-Hung" last="Chan">Kwok-Hung Chan</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology, The University of Hong Kong</s1>
<s3>HKG</s3>
<sZ>1 aut.</sZ>
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<sZ>11 aut.</sZ>
<sZ>13 aut.</sZ>
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<country>Hong Kong</country>
<wicri:noRegion>Department of Microbiology, The University of Hong Kong</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research Center of Infection and Immunology, The University of Hong Kong</s1>
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<sZ>9 aut.</sZ>
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<country>Hong Kong</country>
<wicri:noRegion>Research Center of Infection and Immunology, The University of Hong Kong</wicri:noRegion>
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<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong</s1>
<s3>HKG</s3>
<sZ>2 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Carol Yu Center for Infection, The University of Hong Kong</s1>
<s3>HKG</s3>
<sZ>2 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Carol Yu Center for Infection, The University of Hong Kong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zheng, Bo Jian" sort="Zheng, Bo Jian" uniqKey="Zheng B" first="Bo-Jian" last="Zheng">Bo-Jian Zheng</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology, The University of Hong Kong</s1>
<s3>HKG</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Department of Microbiology, The University of Hong Kong</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research Center of Infection and Immunology, The University of Hong Kong</s1>
<s3>HKG</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>13 aut.</sZ>
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<country>Hong Kong</country>
<wicri:noRegion>Research Center of Infection and Immunology, The University of Hong Kong</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong</s1>
<s3>HKG</s3>
<sZ>2 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Zhao, Guo Ping" sort="Zhao, Guo Ping" uniqKey="Zhao G" first="Guo-Ping" last="Zhao">Guo-Ping Zhao</name>
<affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Chinese National Human Genome Center at Shanghai</s1>
<s3>CHN</s3>
<sZ>3 aut.</sZ>
<sZ>12 aut.</sZ>
</inist:fA14>
<country>République populaire de Chine</country>
<wicri:noRegion>Chinese National Human Genome Center at Shanghai</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Yuen, Kwok Yung" sort="Yuen, Kwok Yung" uniqKey="Yuen K" first="Kwok-Yung" last="Yuen">Kwok-Yung Yuen</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Department of Microbiology, The University of Hong Kong</s1>
<s3>HKG</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>6 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Department of Microbiology, The University of Hong Kong</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Research Center of Infection and Immunology, The University of Hong Kong</s1>
<s3>HKG</s3>
<sZ>1 aut.</sZ>
<sZ>2 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Research Center of Infection and Immunology, The University of Hong Kong</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong</s1>
<s3>HKG</s3>
<sZ>2 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Carol Yu Center for Infection, The University of Hong Kong</s1>
<s3>HKG</s3>
<sZ>2 aut.</sZ>
<sZ>9 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>13 aut.</sZ>
</inist:fA14>
<country>Hong Kong</country>
<wicri:noRegion>Carol Yu Center for Infection, The University of Hong Kong</wicri:noRegion>
</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="2012">2012</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>Infection</term>
<term>Influenzavirus A(H1N1)</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Infection</term>
<term>Antigène CD55</term>
<term>Virus grippal A(H1N1)</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Infection due to 2009 pandemic H1N1 influenza A virus (A[H1N1]pdm09) is commonly manifested as mild infection but occasionally as severe pneumonia. We hypothesized that host genetic variations may contribute to disease severity. An initially small-scale genome-wide association study guided the selection of CD55 single-nucleotide polymorphisms in 425 Chinese patients with severe (n = 177) or mild (n = 248) disease. Carriers of rs2564978 genotype T/T were significantly associated with severe infection (odds ratio, 1.75; P = .011) under a recessive model, after adjustment for clinical confounders. An allele-specific effect on CD55 expression was revealed and ascribed to a promoter indel variation, which was in complete linkage disequilibrium with rs2564978. The promoter variant with deletion exhibited significantly lower transcriptional activity. We further demonstrated that CD55 can protect respiratory epithelial cells from complement attack. Additionally, A(H1N1)pdm09 infection promoted CD55 expression. In conclusion, CD55 polymorphisms are associated with severe A(H1N1)pdm09 infection. CD55 may exert a substantial impact on the disease severity of A (H1N1)pdm09 infection.</div>
</front>
</TEI>
</record>
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