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      Transcriptional Profiling of Host Gene Expression in Chicken Embryo Fibroblasts Infected with Reticuloendotheliosis Virus Strain HA1101

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          Abstract

          Reticuloendotheliosis virus (REV), a member of the Gammaretrovirus genus in the Retroviridae family, causes an immunosuppressive, oncogenic and runting-stunting syndrome in multiple avian hosts. To better understand the host interactions at the transcriptional level, microarray data analysis was performed in chicken embryo fibroblast cells at 1, 3, 5, and 7 days after infection with REV. This study identified 1,785 differentially expressed genes that were classified into several functional groups including signal transduction, immune response, biological adhesion and endocytosis. Significant differences were mainly observed in the expression of genes involved in the immune response, especially during the later post-infection time points. These results revealed that differentially expressed genes IL6, STAT1, MyD88, TLRs, NF-κB, IRF-7, and ISGs play important roles in the pathogenicity of REV infection. Our study is the first to use microarray analysis to investigate REV, and these findings provide insights into the underlying mechanisms of the host antiviral response and the molecular basis of viral pathogenesis.

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          Most cited references55

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          Interferon-stimulated genes: roles in viral pathogenesis

          Highlights • Individual ISGs have measurable phenotypes in vivo. • ISGs control viral pathogenesis through a variety of mechanisms. • ISG effects in vivo are often virus-specific, cell-specific, and tissue-specific.
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            IL-6 signaling in psoriasis prevents immune suppression by regulatory T cells.

            T memory/effector cells (Tmem/eff) isolated from psoriatic patients are chronically activated and poorly suppressed by regulatory T cells (Treg). The proinflammatory cytokine IL-6, which signals through Stat3, allows escape of Tmem/eff cells from Treg-mediated suppression in a murine system. We show here that IL-6 protein is markedly elevated and most highly expressed by CD31(+) endothelial cells and CD11c(+) dermal dendritic cells (DCs) in lesional psoriatic skin. We hypothesized that exposure to high IL-6 in lesional tissue may lead to the dampened Treg function observed in psoriasis patients. Indeed, we found that IL-6, but not other Stat3-activating cytokines, was necessary and sufficient to reverse human T cell suppression by Treg in an in vitro model using activated DCs as a source of IL-6. IL-6Ralpha and gp130 expression was significantly elevated in psoriatic effector T cells compared with normal controls. Overall, IL-6Ralpha expression on Treg exceeded that of effector T cells, and both populations phosphorylated Stat3 in response to IL-6. Phosphorylation of Stat3 in T cells contributes to Th17 differentiation and we identify cells within lesional tissue that coexpress CD3, IL-17, and IL-6, indicating that Th17 cells are present in vivo within the psoriatic Tmem/eff population and contribute to IL-6-mediated resistance to Treg suppression. Taken together, T lymphocytes trafficking into lesional psoriatic skin encounter high IL-6 from endothelial cells, DCs, and Th17 cells, enabling cutaneous T cell escape from Treg suppression and Th17 participation in inflammation. Targeting IL-6 signaling pathways in psoriasis may rebalance Treg/T effector activity and ameliorate disease.
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              A virological view of innate immune recognition.

              The innate immune system uses multiple strategies to detect viral infections. Because all viruses rely on host cells for their synthesis and propagation, the molecular features used to detect viral infections must be unique to viruses and absent from host cells. Research in the past decade has advanced our understanding of various cell-intrinsic and cell-extrinsic modes of virus recognition. This review examines the innate recognition from the point of view of virus invasion and replication strategies, and places innate sensors in the context of detecting viral genome, replication intermediate, transcriptional by-product, and other viral invasion strategies. On the basis of other unique features common to viral infections, undiscovered areas of virus detection are discussed.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 May 2015
                2015
                : 10
                : 5
                : e0126992
                Affiliations
                [1 ]Ministry of Education Key Laboratory for Avian Preventive Medicine, Yangzhou University, Yangzhou, Jiangsu Province, China
                [2 ]Key Laboratory of Jiangsu Preventive Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu Province, China
                [3 ]Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou University, Yangzhou, Jiangsu Province, China
                Public Health Research Institute at RBHS, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AQ JM. Performed the experiments: JM. Analyzed the data: JM AQ JY HS KQ. Contributed reagents/materials/analysis tools: JM YB. Wrote the paper: JM AQ JY.

                Article
                PONE-D-14-58106
                10.1371/journal.pone.0126992
                4431687
                25973612
                bc9f200f-fbc6-4bff-be6e-c86a15b25cca
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 4 January 2015
                : 9 April 2015
                Page count
                Figures: 4, Tables: 5, Pages: 15
                Funding
                Funding provided by the Priority Academic Program Development of Jiangsu Higher Education Institutions, http://www.ec.js.edu.cn/col/col11321/index.html, AQ; 2013FY113300-4, http://www.most.gov.cn/kjjh/gjkjjh/, AQ. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                Data are available from GenBank (Accession number KF305089.1).

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                Uncategorized

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