Identifying antigenicity-associated sites in highly pathogenic H5N1 influenza virus hemagglutinin by using sparse learning.

Identifying antigenicity-associated sites in highly pathogenic H5N1 influenza virus hemagglutinin by using sparse learning.
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DOI:
10.1016/j.jmb.2012.05.011
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发表时间:
2012-09-07
影响因子:
5.6
通讯作者:
Wan, Xiu-Feng
Wan, Xiu-Feng
中科院分区:
生物学2区
文献类型:
--
作者:
Cai, Zhipeng;Ducatez, Mariette F.;Yang, Jialiang;Zhang, Tong;Long, Li-Ping;Boon, Adrianus C.;Webby, Richard J.;Wan, Xiu-Feng

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自我国南方养殖鹅群中分离到A/goose/Guangdong/1/1996(H5 N1)禽流感病毒以来,高致病性H5 N1禽流感病毒一直对公众和动物健康构成威胁。H5血凝素基因的非同义突变导致抗原漂移,给临床诊断和疫苗株筛选带来困难。确定H5 N1的抗原特性将有助于解决这些问题。在这项研究中,开发了一种新的稀疏学习方法,以基于免疫学数据集(即,来自血凝抑制和微量中和测定)和HA蛋白序列。确定了21个潜在的抗原性相关位点。总共使用了17个H5 N1突变体来验证这些预测位点中的11个对H5 N1抗原性的影响,包括7个新鉴定的位点,这些位点不位于已报道的抗体结合位点中。实验数据证实了这些位点的突变导致病毒抗原性的改变,验证了我们的方法。
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 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 datasets (i.e., from hemagglutination inhibition and microneutralization assays) and HA protein sequences. Twenty-one potential antigenicity associated sites were identified. A total of seventeen H5N1 mutants were used to validate the effects of eleven of these predicted sites on H5N1’s antigenicity, including seven 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.
DOI: 10.1073/pnas.0903427106
发表时间: 2009-05-26
影响因子: 11.1
作者:
Ndifon, Wilfred;Wingreen, Ned S.;Levin, Simon A.
通讯作者: Levin, Simon A.
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发表时间: 2010-10-07
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发表时间: 2011-01-04
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发表时间: 2008-10-25
期刊: VIROLOGY
影响因子: 3.7
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