| The human respiratory syncytial virus non-structural protein 1 regulates type I and type II interferon pathways. | |
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MedLine Citation:
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PMID: 22322095 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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SUMMARYRespiratory syncytial viruses encode a non-structural protein (NS1) that interferes with type I and III interferon and other antiviral responses. Proteomic studies were conducted on human A549 type II alveolar epithelial cells and type I interferon-deficient Vero cells (African green monkey kidney cells) infected with wild-type and NS1-deficient clones of human respiratory syncytial virus in order to identify other potential pathway and moleculartargets of NS1 interference. These analyses included 2D-DIGE and quantitative Western blotting. Surprisingly, NS1 was found to suppress the induction of Mn superoxide dismutase (SOD2) expression in A549 cells and to a much lesser degree Vero cells in response to infection. Since SOD2 is not directly inducible by type I interferons it served as a marker to probe the impact of NS1 on signalling of other cytokines known to induce SOD2 expression and/or indirect effects of type I interferon signalling. Deductiveanalysis of results obtained from cell infection and cytokine stimulation studiesindicated that interferon-γ signalling was a potential target of NS1, possibly as a result of modulation of STAT1 levels. However, this was not sufficient to explain the magnitude of the impact of NS1 on SOD2 induction in A549 cells. Vero cell infection experiments indicated that NS1 targeted a component ofthe type I interferon response that does not directly induce SOD2 expression but is required to induce another initiator of SOD2 expression. STAT2 was ruled out as a target of NS1 interference using quantitative Western blot analysis of infected A549 cells but data were obtained to indicate that STAT1was one of a number of potential targets of NS1. A label-free mass spectrometry-based quantitative approach is proposed as a means of more definitive identification of NS1 targets. |
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Authors:
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Marcus L Hastie; Madeleine J Headlam; Nirav B Patel; Alexander A Bukreyev; Ursula J Buchholz; Keyur A Dave; Emma L Norris; Cassandra L Wright; Kirsten M Spann; Peter L Collins; Jeffrey J Gorman |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-8 |
Journal Detail:
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Title: Molecular & cellular proteomics : MCP Volume: - ISSN: 1535-9484 ISO Abbreviation: - Publication Date: 2012 Feb |
Date Detail:
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Created Date: 2012-2-10 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101125647 Medline TA: Mol Cell Proteomics Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Queensland Institute of Medical Research, Australia; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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