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      Clinical Correlations of Transcriptional Profile in Patients Infected With Avian Influenza H7N9 Virus

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          Abstract

          This study correlated serial blood transcriptomic profiles of patients with avian influenza A (H7N9) virus infection with clinical data of patients. Biologically significant transcriptomic profiles associated with blood oxygenation and viral load in the lower respiratory tract were defined.

          Abstract

          Background

          Avian influenza A (H7N9) viruses emerged in China in 2013 and caused zoonotic disease associated with a case-fatality ratio of over 30%. Transcriptional profiles in peripheral blood reflect host responses and can help to elucidate disease pathogenesis.

          Methods

          We correlated serial blood transcriptomic profiles of patients with avian influenza A (H7N9) virus infection and determined the biological significances from the analysis.

          Results

          We found that specific gene expression profiles in the blood were strongly correlated with the Pao 2/Fio 2 ratio and viral load in the lower respiratory tract. Cell cycle and leukocyte-related immunity were activated at the acute stage of the infection while T-cell functions and various metabolic processes were associated with the recovery phase of the illness. A transition from systemic innate to adaptive immunity was found.

          Conclusions

          We developed a novel approach for transcriptomic analysis to identify key host responses that were strongly correlated with specific clinical and virologic parameters in patients with H7N9 infection.

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          Most cited references24

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          Human Infection with a Novel Avian-Origin Influenza A (H7N9) Virus

          New England Journal of Medicine, 368(20), 1888-1897
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            Biological features of novel avian influenza A (H7N9) virus.

            Human infection associated with a novel reassortant avian influenza H7N9 virus has recently been identified in China. A total of 132 confirmed cases and 39 deaths have been reported. Most patients presented with severe pneumonia and acute respiratory distress syndrome. Although the first epidemic has subsided, the presence of a natural reservoir and the disease severity highlight the need to evaluate its risk on human public health and to understand the possible pathogenesis mechanism. Here we show that the emerging H7N9 avian influenza virus poses a potentially high risk to humans. We discover that the H7N9 virus can bind to both avian-type (α2,3-linked sialic acid) and human-type (α2,6-linked sialic acid) receptors. It can invade epithelial cells in the human lower respiratory tract and type II pneumonocytes in alveoli, and replicated efficiently in ex vivo lung and trachea explant culture and several mammalian cell lines. In acute serum samples of H7N9-infected patients, increased levels of the chemokines and cytokines IP-10, MIG, MIP-1β, MCP-1, IL-6, IL-8 and IFN-α were detected. We note that the human population is naive to the H7N9 virus, and current seasonal vaccination could not provide protection.
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              Empirical bayes methods and false discovery rates for microarrays.

              In a classic two-sample problem, one might use Wilcoxon's statistic to test for a difference between treatment and control subjects. The analogous microarray experiment yields thousands of Wilcoxon statistics, one for each gene on the array, and confronts the statistician with a difficult simultaneous inference situation. We will discuss two inferential approaches to this problem: an empirical Bayes method that requires very little a priori Bayesian modeling, and the frequentist method of "false discovery rates" proposed by Benjamini and Hochberg in 1995. It turns out that the two methods are closely related and can be used together to produce sensible simultaneous inferences. Copyright 2002 Wiley-Liss, Inc.
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                Author and article information

                Journal
                J Infect Dis
                J. Infect. Dis
                jid
                The Journal of Infectious Diseases
                Oxford University Press (US )
                0022-1899
                1537-6613
                15 October 2018
                28 May 2018
                28 May 2018
                : 218
                : 8
                : 1238-1248
                Affiliations
                [1 ]State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University
                [2 ]Hong Kong University-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong
                [3 ]Department of Emergency and Critical Care Medicine, Guangdong General Hospital, Guangdong Academy of Medical Sciences
                [4 ]Dongguan People’s Hospital, China
                [5 ]Department of Integrative Structural and Computational Biology
                [6 ]Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, California
                [7 ]Institute for Cellular and Molecular Biology, University of Texas at Austin
                Author notes

                W. G., Z. Y. and N. C. W. contributed equally.

                Correspondence: C. K. P. Mok, PhD, The First Affiliated Hospital of Guangzhou Medical University, No.151, Yanjiangxi Road, Guangzhou, Guangdong, China ( ch02mkp@ 123456hku.hk ).
                Article
                jiy317
                10.1093/infdis/jiy317
                6129114
                29846612
                99f0f5dd-1a2b-468b-9118-3056ceae5274
                © The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

                History
                : 06 February 2018
                : 24 May 2018
                Page count
                Pages: 11
                Funding
                Funded by: National Natural Science Foundation of China 10.13039/501100001809
                Award ID: 81761128014
                Funded by: Science Research Project of the Guangdong Province
                Award ID: 2016A050503047
                Funded by: Municipal Science and Technology Bureau Foundation of Guangzhou
                Award ID: 2014Y2-00031
                Funded by: Research Grants Council of the Hong Kong Special Administrative Region, China
                Award ID: T11-705/14N
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: R56 AI127371
                Funded by: Croucher Foundation 10.13039/501100001692
                Categories
                Major Articles and Brief Reports
                Viruses

                Infectious disease & Microbiology
                h7n9,avian influenza,pa,o,2/ f,io,2,transcriptomic
                Infectious disease & Microbiology
                h7n9, avian influenza, pa, o, 2/ f, io, 2, transcriptomic

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