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Exogenous nef induces proinflammatory signaling events in murine macrophages.
Mangino, Giorgio; Serra, Valeria; Borghi, Paola; Percario, Zulema A; Horenkamp, Florian A; Geyer, Matthias; Affabris, Elisabetta.
Afiliação
  • Mangino G; Department of Biology, University Roma Tre, Rome, Italy.
Viral Immunol ; 25(2): 117-30, 2012 Apr.
Article em En | MEDLINE | ID: mdl-22413916
ABSTRACT
Despite the fact that murine cells are not permissive for human immunodeficiency virus type 1 (HIV-1) infection, several investigators have constructed transgenic (Tg) mice to model HIV-1-induced diseases to overcome this restriction. The generation of Tg mice expressing selected HIV-1 genes revealed that Nef harbors a major disease determinant. HIV-1 Nef protein is a molecular adapter able to interact with several cellular partners, interfering with cellular functions. The phenotype of Nef Tg mice was extensively characterized regarding in vivo development of AIDS-like disease and the effects of Nef expression in T lymphocytes, but the functions eventually corrupted by Nef in monocytes and macrophages were less studied. Nef treatment of human monocyte-derived macrophages induces the internalization of the protein and modulates the production and secretion of different chemokines and cytokines by activating specific intracellular signaling pathways (i.e., NF-κB, MAPK, and IRF3). Therefore we set up an in vitro murine macrophage-based model using stabilized cell lines and primary peritoneal macrophages, and treated them with recombinant myristoylated Nef(SF2) (recNef). Like human cells, murine macrophages responded to Nef treatment, activating IKK-α and IKK-ß, JNK, and p38 MAP kinases. Activation of the NF-κB pathway is mandatory for the synthesis and release of a pool of cytokines and chemokines, including IFN-ß, that induce tyrosine phosphorylation of the signal transducer and activator of transcription (STAT)-1, STAT-2, and STAT-3, in an autocrine and paracrine manner, confirming that murine macrophages respond to Nef similarly to human ones. These data extend the results previously obtained in human primary macrophages, allowing the use of murine cells in culture to study signaling events modulated by Nef in myeloid-derived cells. In particular, it may be feasible to use macrophages derived from mice knocked out in specific signaling intermediates to obtain greater insight into the mechanism of Nef-induced effects.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / HIV-1 / Fatores de Virulência / Produtos do Gene nef do Vírus da Imunodeficiência Humana / Ativação de Macrófagos / Macrófagos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Viral Immunol Assunto da revista: ALERGIA E IMUNOLOGIA / VIROLOGIA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Itália

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / HIV-1 / Fatores de Virulência / Produtos do Gene nef do Vírus da Imunodeficiência Humana / Ativação de Macrófagos / Macrófagos Tipo de estudo: Prognostic_studies Limite: Animals / Humans Idioma: En Revista: Viral Immunol Assunto da revista: ALERGIA E IMUNOLOGIA / VIROLOGIA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Itália