Identifying Antigenicity-Associated Sites in Highly Pathogenic H5N1 Influenza Virus Hemagglutinin by Using Sparse Learning

被引:38
作者
Cai, Zhipeng [1 ]
Ducatez, Mariette F. [2 ]
Yang, Jialiang [1 ]
Zhang, Tong [3 ]
Long, Li-Ping [1 ]
Boon, Adrianus C. [2 ]
Webby, Richard J. [2 ]
Wan, Xiu-Feng [1 ]
机构
[1] Mississippi State Univ, Coll Vet Med, Dept Basic Sci, Mississippi State, MS 39762 USA
[2] St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA
[3] Rutgers State Univ, Dept Stat & Biostat, Piscataway, NJ 08854 USA
关键词
antibody binding site; antigenicity; sparse learning; antigenic drift; H5N1; AVIAN INFLUENZA; MONOCLONAL-ANTIBODY; STRUCTURAL BASIS; SOUTHERN CHINA; ESCAPE MUTANT; EVOLUTION; NEURAMINIDASE; GENERATION; DIVERSITY; SELECTION;
D O I
10.1016/j.jmb.2012.05.011
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Since the isolation of A/goose/Guangdong/1/1996 (H5N1) in farmed geese in southern China, highly pathogenic H5N1 avian influenza viruses have posed a continuous threat to both public and animal health. The non-synonymous mutation of the H5 hemagglutinin (HA) gene has resulted in antigenic drift, leading to difficulties in both clinical diagnosis and vaccine strain selection. Characterizing H5N1's antigenic profiles would help resolve these problems. In this study, a novel sparse learning method was developed to identify antigenicity-associated sites in influenza A viruses on the basis of immunologic data sets (i.e., from hemagglutination inhibition and micro-neutralization assays) and HA protein sequences. Twenty-one potential antigenicity-associated sites were identified. A total of 17 H5N1 mutants were used to validate the effects of 11 of these predicted sites on H5N1's antigenicity, including 7 newly identified sites not located in reported antibody binding sites. The experimental data confirmed that mutations of these tested sites lead to changes in viral antigenicity, validating our method. (C) 2012 Elsevier Ltd. All rights reserved.
引用
收藏
页码:145 / 155
页数:11
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