Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection.
Glycomic analysis of human respiratory tract tissues and correlation with influenza virus infection.
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人类呼吸道组织的糖分析以及与流感病毒感染的相关性。
DOI：
10.1371/journal.ppat.1003223
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发表时间：
2013-03
期刊：
影响因子：
6.7
通讯作者：
Nicholls JM
中科院分区：
文献类型：
--
作者：
Walther T;Karamanska R;Chan RW;Chan MC;Jia N;Air G;Hopton C;Wong MP;Dell A;Malik Peiris JS;Haslam SM;Nicholls JM
流感病毒感染人呼吸道的第一步是病毒与唾液酸（Sia）末端受体结合。不同病毒株与受体的结合由唾液酸与半乳糖的α键和相邻聚糖结构决定。在本研究中，通过质谱法表征了人肺、支气管和鼻咽的N-和O-聚糖组成。分析表明，在肺和支气管中存在广谱Sia α2-3和α2-6聚糖。然后将该聚糖结构数据与4种已发表的聚糖阵列的结合数据结合使用，以评估这些当前的聚糖阵列是否能够预测人类、鸟类和猪病毒在人类离体呼吸道组织中的复制。来自功能性糖组学联盟的最全面的阵列包含最大多样性的唾液酸化聚糖，但不能预测支气管和肺中的生产性复制。我们的研究结果表明，更全面，但重点阵列需要开发调查流感病毒结合在评估新出现的流感病毒。本研究旨在确定人类呼吸道中存在哪些可能的流感聚糖受体。我们将现有已发表的聚糖阵列上存在的聚糖与通过质谱分析在人呼吸道中鉴定的实际聚糖进行了比较，以确定这些阵列在潜在结合方面的代表性。迄今为止最全面的阵列仅包含存在的实际聚糖范围的大约一半。在过去5年中，我们用季节性、禽流感和猪流感病毒对113个支气管和185个肺样本进行了离体感染，并证明肺能够被所有类型的流感病毒感染，但支气管也可以被有限范围的禽流感、猪流感和季节性病毒感染。关键发现是呼吸道中存在广谱聚糖，流感病毒可利用这些聚糖进行感染，目前可用的阵列无法预测成功感染。我们的研究结果将有助于研究人员开发更全面和更有针对性的阵列，用于筛选新出现的流感病毒和细菌，以确定它们对人类的潜在威胁。
The first step in influenza infection of the human respiratory tract is binding of the virus to sialic (Sia) acid terminated receptors. The binding of different strains of virus for the receptor is determined by the α linkage of the sialic acid to galactose and the adjacent glycan structure. In this study the N- and O-glycan composition of the human lung, bronchus and nasopharynx was characterized by mass spectrometry. Analysis showed that there was a wide spectrum of both Sia α2-3 and α2-6 glycans in the lung and bronchus. This glycan structural data was then utilized in combination with binding data from 4 of the published glycan arrays to assess whether these current glycan arrays were able to predict replication of human, avian and swine viruses in human ex vivo respiratory tract tissues. The most comprehensive array from the Consortium for Functional Glycomics contained the greatest diversity of sialylated glycans, but was not predictive of productive replication in the bronchus and lung. Our findings indicate that more comprehensive but focused arrays need to be developed to investigate influenza virus binding in an assessment of newly emerging influenza viruses. This study was performed to determine what possible glycan receptors for influenza were present in the human respiratory tract. We compared the glycans present on existing published glycan arrays with the actual glycans identified in the human respiratory tract by mass spectrometric analysis to determine how representative these arrays would be for potential binding. The most comprehensive array to date only contained approximately half the range of the actual glycans present. Over the past 5 years we have performed ex-vivo infection of 113 bronchial and 185 lung samples with seasonal, avian and swine influenza viruses, and have demonstrated that the lung is able to be infected by all types of influenza viruses but that the bronchus can also be infected by a limited range of avian, swine and seasonal viruses. The key findings are that there is wide spectrum of glycans present in the respiratory tract which can be used by influenza viruses for infection, and the currently available arrays are not predictive of successful infection. Our findings will be of use for researchers in developing more comprehensive and focused arrays for the screening of emerging influenza viruses and bacteria in order to determine their potential threat to humans.
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DOI：
10.1074/jbc.m110.115998
发表时间：
2010-10-29
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Bateman AC;Karamanska R;Busch MG;Dell A;Olsen CW;Haslam SM
通讯作者：
Haslam SM
DOI：
10.2353/ajpath.2010.100115
发表时间：
2010-07
期刊：
The American journal of pathology
影响因子：
--
作者：
Shieh WJ;Blau DM;Denison AM;Deleon-Carnes M;Adem P;Bhatnagar J;Sumner J;Liu L;Patel M;Batten B;Greer P;Jones T;Smith C;Bartlett J;Montague J;White E;Rollin D;Gao R;Seales C;Jost H;Metcalfe M;Goldsmith CS;Humphrey C;Schmitz A;Drew C;Paddock C;Uyeki TM;Zaki SR
通讯作者：
Zaki SR
影响因子：
5.4
作者：
Chan, Renee W. Y.;Kang, Sara S. R.;Chan, Michael C. W.
通讯作者：
Chan, Michael C. W.
影响因子：
3
作者：
Morelle, W;Sutton-Smith, M;Dell, A
通讯作者：
Dell, A
影响因子：
4.8
作者：
Kumari, Kshama;Gulati, Shelly;Air, Gillian M.
通讯作者：
Air, Gillian M.