ADP ribosylation factor 1 activity is required to recruit AP-1 to the major histocompatibility complex class I (MHC-I) cytoplasmic tail and disrupt MHC-I trafficking in HIV-1-infected primary T cells.
J Virol
; 85(23): 12216-26, 2011 Dec.
Article
em En
| MEDLINE
| ID: mdl-21917951
ABSTRACT
HIV-1-infected cells are partially resistant to anti-HIV cytotoxic T lymphocytes (CTLs) due to the effects of the HIV Nef protein on antigen presentation by major histocompatibility complex class I (MHC-I), and evidence has been accumulating that this function of Nef is important in vivo. HIV Nef disrupts the normal expression of MHC-I by stabilizing a protein-protein interaction between the clathrin adaptor protein AP-1 and the MHC-I cytoplasmic tail. There is also evidence that Nef activates a phosphatidylinositol 3 kinase (PI3K)-dependent GTPase, ADP ribosylation factor 6 (ARF-6), to stimulate MHC-I internalization. However, the relative importance of these two pathways is unclear. Here we report that a GTPase required for AP-1 activity (ARF-1) was needed for Nef to disrupt MHC-I surface levels, whereas no significant requirement for ARF-6 was observed in Nef-expressing T cell lines and in HIV-infected primary T cells. An ARF-1 inhibitor blocked the ability of Nef to recruit AP-1 to the MHC-I cytoplasmic tail, and a dominant active ARF-1 mutant stabilized the Nef-MHC-I-AP-1 complex. These data support a model in which Nef and ARF-1 stabilize an interaction between MHC-I and AP-1 to disrupt the presentation of HIV-1 epitopes to CTLs.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Linfócitos T
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Infecções por HIV
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Antígeno HLA-A2
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Fator de Transcrição AP-1
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Fatores de Ribosilação do ADP
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Fator 1 de Ribosilação do ADP
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
J Virol
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos