HIV-1 Nef induces proinflammatory state in macrophages through its acidic cluster domain: involvement of TNF alpha receptor associated factor 2
| Autor: | Giovanna Romeo, Alessia Noto, Gabriele Vaccari, Matthias Geyer, Zulema A. Percario, Santiago Manrique, Filippo Acconcia, Cristiano Chiarabelli, Gianna Fiorucci, Fabio Polticelli, Florian A. Horenkamp, Giorgio Mangino, Stefano Leone, Elisabetta Affabris |
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| Přispěvatelé: | Mangino, G, Percario, ZULEMA ANTONIA, Fiorucci, G, Vaccari, G, Acconcia, Filippo, Chiarabelli, Cristiano, Leone, Stefano, Noto, Alessia, Horenkamp, Fa, Manrique, S, Romeo, G, Polticelli, Fabio, Geyer, M, Affabris, Elisabetta |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
TRAF2
Chemokine Signal transduction Biochemistry Myristic Acid Monocytes chemistry.chemical_compound Molecular cell biology Immunodeficiency Viruses Membrane Receptor Signaling Multidisciplinary biology NF-kappa B Transcriptional signaling macrophages Cell biology Host-Pathogen Interaction STAT Transcription Factors molecular virology Cytokines Infectious diseases Medicine Tumor necrosis factor alpha Chemokines Inflammation Mediators Immunologic Receptor Signaling Research Article Protein Binding Immune Cells Science DNA transcription Immunology Signaling in cellular processes Molecular Sequence Data Retrovirology and HIV immunopathogenesis Viral diseases Microbiology Proinflammatory cytokine Molecular Genetics Structure-Activity Relationship Virology DNA-binding proteins Consensus Sequence Genetics Humans Gene Regulation Amino Acid Sequence nef Gene Products Human Immunodeficiency Virus Phosphotyrosine Biology Transcription factor STAT signaling family Inflammation TNF Receptor-Associated Factor 6 Binding Sites Nef CD40 Interleukin-6 Tumor Necrosis Factor-alpha Immunity Proteins HIV Tyrosine phosphorylation Interferon-beta virus-cell interactions TNF Receptor-Associated Factor 2 NFKB1 Molecular biology Protein Structure Tertiary Gene Expression Regulation TRAFs chemistry Immune System Virulence Factors and Mechanisms Mutation HIV-1 biology.protein Interferon Regulatory Factor-3 Gene expression |
| Zdroj: | PLoS ONE, Vol 6, Iss 8, p e22982 (2011) PloS one 6 (2011): e22982. doi:10.1371/journal.pone.0022982 info:cnr-pdr/source/autori:Mangino G, Percario ZA, Fiorucci G, Vaccari G, Acconcia F, Chiarabelli C, Leone S, Noto A, Horenkamp FA, Manrique S, Romeo G, Polticelli F, Geyer M, Affabris E./titolo:HIV-1 Nef induces proinflammatory state in macrophages through its acidic cluster domain: involvement of TNF alpha receptor associated factor 2/doi:10.1371%2Fjournal.pone.0022982/rivista:PloS one/anno:2011/pagina_da:e22982/pagina_a:/intervallo_pagine:e22982/volume:6 PLoS ONE |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0022982 |
| Popis: | ""Background: HIV-1 Nef is a virulence factor that plays multiple roles during HIV replication. Recently, it has been described. that Nef intersects the CD40 signalling in macrophages, leading to modification in the pattern of secreted factors that. appear able to recruit, activate and render T lymphocytes susceptible to HIV infection. The engagement of CD40 by CD40L. induces the activation of different signalling cascades that require the recruitment of specific tumor necrosis factor. receptor-associated factors (i.e. TRAFs). We hypothesized that TRAFs might be involved in the rapid activation of NF-kB,. MAPKs and IRF-3 that were previously described in Nef-treated macrophages to induce the synthesis and secretion of. proinflammatory cytokines, chemokines and IFNbeta to activate STAT1, -2 and -3.. Methodology\\\/Principal Findings: Searching for possible TRAF binding sites on Nef, we found a TRAF2 consensus binding. site in the AQEEEE sequence encompassing the conserved four-glutamate acidic cluster. Here we show that all the. signalling effects we observed in Nef treated macrophages depend on the integrity of the acidic cluster. In addition, Nef was. able to interact in vitro with TRAF2, but not TRAF6, and this interaction involved the acidic cluster. Finally silencing. experiments in THP-1 monocytic cells indicate that both TRAF2 and, surprisingly, TRAF6 are required for the Nef-induced. tyrosine phosphorylation of STAT1 and STAT2.. Conclusions: Results reported here revealed TRAF2 as a new possible cellular interactor of Nef and highlighted that in. monocytes\\\/macrophages this viral protein is able to manipulate both the TRAF\\\/NF-kB and TRAF\\\/IRF-3 signalling axes,. thereby inducing the synthesis of proinflammatory cytokines and chemokines as well as IFNbeta."" |
| Databáze: | OpenAIRE |
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