The interactome of the human respiratory syncytial virus NS1 protein highlights multiple effects on host cell biology. 2012

Weining Wu, and Kim C Tran, and Michael N Teng, and Kate J Heesom, and David A Matthews, and John N Barr, and Julian A Hiscox
School of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, United Kingdom.

Viral proteins can have multiple effects on host cell biology. Human respiratory syncytial virus (HRSV) nonstructural protein 1 (NS1) is a good example of this. During the virus life cycle, NS1 can act as an antagonist of host type I and III interferon production and signaling, inhibit apoptosis, suppress dendritic cell maturation, control protein stability, and regulate transcription of host cell mRNAs, among other functions. It is likely that NS1 performs these different roles through interactions with multiple host cell proteins. To investigate this and identify cellular proteins that could interact with NS1, we used quantitative proteomics in combination with green fluorescent protein (GFP)-trap immunoprecipitation and bioinformatic analysis. This analysis identified 221 proteins that were potentially part of complexes that could interact with NS1, with many of these associated with transcriptional regulation as part of the mediator complex, cell cycle regulation, and other functions previously assigned to NS1. Specific immunoprecipitation using the GFP trap was used to confirm the ability of selected cellular proteins to interact individually with NS1. Infection of A549 cells with recombinant viruses deficient in the expression of NS1 and overexpression analysis both demonstrated that NS1 was necessary and sufficient for the enrichment of cells in the G(1) phase of the cell cycle.

UI MeSH Term Description Entries
D007370 Interferon Type I Interferon secreted by leukocytes, fibroblasts, or lymphoblasts in response to viruses or interferon inducers other than mitogens, antigens, or allo-antigens. They include alpha- and beta-interferons (INTERFERON-ALPHA and INTERFERON-BETA). Interferons Type I,Type I Interferon,Type I Interferons,Interferon, Type I,Interferons, Type I
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003713 Dendritic Cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION). Dendritic Cells, Interdigitating,Interdigitating Cells,Plasmacytoid Dendritic Cells,Veiled Cells,Dendritic Cells, Interstitial,Dendritic Cells, Plasmacytoid,Interdigitating Dendritic Cells,Interstitial Dendritic Cells,Cell, Dendritic,Cell, Interdigitating,Cell, Interdigitating Dendritic,Cell, Interstitial Dendritic,Cell, Plasmacytoid Dendritic,Cell, Veiled,Cells, Dendritic,Cells, Interdigitating,Cells, Interdigitating Dendritic,Cells, Interstitial Dendritic,Cells, Plasmacytoid Dendritic,Cells, Veiled,Dendritic Cell,Dendritic Cell, Interdigitating,Dendritic Cell, Interstitial,Dendritic Cell, Plasmacytoid,Interdigitating Cell,Interdigitating Dendritic Cell,Interstitial Dendritic Cell,Plasmacytoid Dendritic Cell,Veiled Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D016193 G1 Phase The period of the CELL CYCLE preceding DNA REPLICATION in S PHASE. Subphases of G1 include "competence" (to respond to growth factors), G1a (entry into G1), G1b (progression), and G1c (assembly). Progression through the G1 subphases is effected by limiting growth factors, nutrients, or inhibitors. First Gap Phase,G1a Phase,G1b Phase,Gap Phase 1,First Gap Phases,G1 Phases,G1a Phases,G1b Phases,Gap Phase, First,Gap Phases, First,Phase 1, Gap,Phase, First Gap,Phase, G1,Phase, G1a,Phase, G1b,Phases, First Gap,Phases, G1,Phases, G1a,Phases, G1b
D017209 Apoptosis A regulated cell death mechanism characterized by distinctive morphologic changes in the nucleus and cytoplasm, including the endonucleolytic cleavage of genomic DNA, at regularly spaced, internucleosomal sites, i.e., DNA FRAGMENTATION. It is genetically programmed and serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. Apoptosis, Extrinsic Pathway,Apoptosis, Intrinsic Pathway,Caspase-Dependent Apoptosis,Classic Apoptosis,Classical Apoptosis,Programmed Cell Death,Programmed Cell Death, Type I,Apoptoses, Extrinsic Pathway,Apoptoses, Intrinsic Pathway,Apoptosis, Caspase-Dependent,Apoptosis, Classic,Apoptosis, Classical,Caspase Dependent Apoptosis,Cell Death, Programmed,Classic Apoptoses,Extrinsic Pathway Apoptoses,Extrinsic Pathway Apoptosis,Intrinsic Pathway Apoptoses,Intrinsic Pathway Apoptosis
D017361 Viral Nonstructural Proteins Proteins encoded by a VIRAL GENOME that are not structural components of VIRUS PARTICLES. Some of these proteins may play roles within the infected cell during VIRUS REPLICATION or act in regulation of virus replication or VIRUS ASSEMBLY. Nonstructural Proteins, Viral,NS Proteins, Viral,Viral NS Proteins,Viral Non-Structural Proteins,Viral Nonstructural Protein,Viral Nonstructural Proteins NS1,Viral Nonstructural Proteins NS2,Nonstructural Protein, Viral,Viral Non Structural Proteins
D018113 Respiratory Syncytial Virus, Human The type species of PNEUMOVIRUS and an important cause of lower respiratory disease in infants and young children. It frequently presents with bronchitis and bronchopneumonia and is further characterized by fever, cough, dyspnea, wheezing, and pallor. HRSV Human respiratory syncytial virus,Human respiratory syncytial virus,human RSV,RSV, human,human RSVs
D018357 Respiratory Syncytial Virus Infections Pneumovirus infections caused by the RESPIRATORY SYNCYTIAL VIRUSES. Humans and cattle are most affected but infections in goats and sheep have been reported. RSV Infection,Infections, Respiratory Syncytial Virus,Respiratory Syncytial Virus Infection,Infection, RSV,RSV Infections

Related Publications

Weining Wu, and Kim C Tran, and Michael N Teng, and Kate J Heesom, and David A Matthews, and John N Barr, and Julian A Hiscox
October 2021, Cell reports,
Weining Wu, and Kim C Tran, and Michael N Teng, and Kate J Heesom, and David A Matthews, and John N Barr, and Julian A Hiscox
September 2017, The Journal of general virology,
Weining Wu, and Kim C Tran, and Michael N Teng, and Kate J Heesom, and David A Matthews, and John N Barr, and Julian A Hiscox
June 2017, Nature microbiology,
Weining Wu, and Kim C Tran, and Michael N Teng, and Kate J Heesom, and David A Matthews, and John N Barr, and Julian A Hiscox
February 2008, Protein expression and purification,
Weining Wu, and Kim C Tran, and Michael N Teng, and Kate J Heesom, and David A Matthews, and John N Barr, and Julian A Hiscox
July 2002, The Journal of infection,
Weining Wu, and Kim C Tran, and Michael N Teng, and Kate J Heesom, and David A Matthews, and John N Barr, and Julian A Hiscox
November 2008, Sheng wu gong cheng xue bao = Chinese journal of biotechnology,
Weining Wu, and Kim C Tran, and Michael N Teng, and Kate J Heesom, and David A Matthews, and John N Barr, and Julian A Hiscox
October 2022, Journal of molecular biology,
Weining Wu, and Kim C Tran, and Michael N Teng, and Kate J Heesom, and David A Matthews, and John N Barr, and Julian A Hiscox
April 2011, PLoS pathogens,
Weining Wu, and Kim C Tran, and Michael N Teng, and Kate J Heesom, and David A Matthews, and John N Barr, and Julian A Hiscox
January 2014, Intervirology,
Weining Wu, and Kim C Tran, and Michael N Teng, and Kate J Heesom, and David A Matthews, and John N Barr, and Julian A Hiscox
November 2011, Bing du xue bao = Chinese journal of virology,
Copied contents to your clipboard!